bluuebunny/crossref_metadata_2025_split huggingface dataset:
INSP-11. Patient-centered monitoring and care of cognitive late effects in pediatric brain tumor survivors with and without Cerebellar Mutism Syndrome (CMS).
Authors: Walsh Karin , Sady Maegan , Tiplady Kaitlyn , van Scoyoc Shawna , Weisman Hannah , Hardy Kristina 
Published: June 2022

Abstract
Risks of cognitive late effects in children with brain tumors is well-established. However, group heterogeneity may limit generalizability and result in inadequate neurocognitive monitoring and care. Children with CMS have unique long-term cognitive risks and current knowledge may not adequately describe their experience or needs. The establishment and implementation of patient-centered, empirically-derived assessment of cognitive change following tumor diagnosis and treatment is a novel, precision-based approach to patient care. METHODS: 30 patients diagnosed with posterior fossa tumor who had at least 2 neuropsychological evaluations were included. Primary outcomes were processing speed (Wechsler PSI) and working memory (WMI). Secondary outcomes were verbal and nonverbal intellect. Reliable change indices (RCIs) were computed (Chelune et al., 1993). Using an 80% CI, 10% would be expected to decline, while 90% would stay stable or improve. RESULTS: Mean age in the full sample was 9.2 (3.32) years at T1 and 13.0 (4.11) years at T2, with an average of 2.7 (2.58) years between assessments. Males made up 56.7% of the sample. Five of the 30 (17%) were CMS+. The CMS+ patients were similar in age to CMS- patients, were predominantly male (80%), and mostly received photon radiation (60%). The full sample showed greater prevalence of declining verbal (21%), spatial (58%) and working memory (29%) functions than the expected (10%). The CMS+ group had higher rates of processing speed (50% v. 7%) and working memory (50% v. 27%) declines than the CMS- group. In contrast, the CMS- group appeared to show more prevalent declines in spatial reasoning than the CMS+ group (67% v. 33%). CONCLUSIONS: There appear to be unique domains impacted in the CMS+ group, which can convey specific long-term outcomes specific to this subgroup of patients. These results highlight the utility of individualized, empirically-driven analysis of change in cognitive functioning in this patient population.
INSP-12. Molecular architecture of the human brain and brain cancer
Authors: Linnarsson Sten 
Published: June 2022

Abstract
Single-cell gene expression analysis has revolutionized biomedical research, leading to comprehensive atlases of human tissues, insights into development and homeostasis and allowed highly multiplexed perturbations with cell type specificity. Here, I present our comprehensive single-cell atlas of the human nervous system, both in development and in the adult. We describe unexpected regional diversity among human glial cell types, with implications for regions-specific glial brain disease. However, in single-cell analysis, spatial context is lost, complicating the analysis of cell-cell interactions, spatial gradients and patterns of cell distribution. Spatial methods of gene expression analysis have therefore increased in importance, and are currently a very active are of research and development. We have developed a scalable and highly multiplexed method of spatial gene expression analysis based on electrophoretic capture of mRNA. I showcase its throughput and robustness by presenting complete spatial atlases of the adult mouse brain, as well as the whole developing human head at 7 weeks post-conception. Furthermore, I will discuss our ongoing work to apply these methods to human glioblastoma in order to reveal the spatial architecture of this devastating tumor.
INSP-13. Malignant networks in brain tumors: from basic discoveries to clinical implications
Authors: Winkler Frank 
Published: June 2022

Abstract
Integration into communicating tumor cell networks is a way how the entire brain tumor organism can progress in the brain, and resist therapies. It started with our discovery of ultra-long membrane protrusions, tumor microtube (TM), in tumor cells from glioblastomas and other incurable adult and pediatric glioma entities (Osswald et al., Nature 2015). These TMs are used for early brain invasion, and later interconnect single tumor cells to communicating and resistant multicellular networks, but also glioma cells to neurons in the brain, with neuron-glioma synapses stimulating glioma progression (Venkataramani et al., Nature 2019). Increasing formation of these homotypic and heterotypic networks is seen with increasing glioma malignancy: lowest in low-grade oligodendrogliomas, and highest in glioblastomas and K27M mutated gliomas. The genetic reduction of GAP-43, a crucial neurodevelopmental factor that drives TM formation and function, not only deprived glioblastoma cells from the ability to form functional tumor networks, but also made radiotherapy much more effective, by and large eradicating experimental tumors from the mouse brain, which is typically not possible with radiotherapy alone. Consistent with the concept of tumor cell resilience by network integration, radiotherapy and also chemotherapy (Weil et al., Neuro-Oncology 2017) preferentially killed the unconnected glioblastoma cells, leaving the tumor cell networks largely intact. Damage to the tumor network by surgical measures induced a self-healing response. Taken together, integration into multicellular, highly functional, communicating and resilient networks is not only a feature of the nervous system, but also of incurable, most aggressive brain tumors. In this talk, clinical concepts that originate from these discoveries are presented, including a network disconnection strategy currently tested in the German MecMeth trial (EudraCT2021-000708-39), and the AMPAR inhibitor perampanel as a potential inhibitor of neuron-glioma synapses. Furthermore, new basic and translational developments in the field of brain tumor networks are presented and discussed.
INSP-16. Focused ultrasound-mediated blood-brain barrier disruption for the treatment of pediatric high-grade glioma
Authors: van Vuurden Dannis , Ries Mario 
Published: June 2022

Abstract
Pediatric patients with high-grade glioma (HGG), such as glioblastoma (GBM) and H3K27M-altered diffuse midline glioma (DMG) suffer from a dismal prognosis and a poor quality of life. So far, no therapeutic strategy has resulted in significant long-term survival benefit for these patients. Drug therapies have largely failed due to inadequate drug delivery to the brain as a result of the blood-brain barrier, preventing most drugs from entering the brain. Intrinsic and acquired tumor heterogeneity, with drug-resistant tumor cell subpopulations add to the therapeutic failure. Furthermore, these tumors evade the immune system by creating a highly tumor-promoting and immunosuppressive tumor immune microenvironment, which is composed of microglia and tumor-associated macrophages. Recently, microbubble-assisted, focused ultrasound-mediated blood-brain barrier disruption (FUS-BBBD) has emerged as a promising and clinically available technology to circumvent part of these problems. FUS-BBBD allows improved delivery of therapeutics (chemotherapy, small molecules, monoclonal antibodies, immunotherapies) to the brain. The technology is emerging both in preclinical and clinical pediatric neuro-oncology research, with invasive and minimally invasive clinical FUS-BBBD systems available for early phase clinical trials. How the right drugs in the optimal combination can be delivered with the best timing (pharmacokinetics) via FUS-BBBD has yet to be ascertained and is subject of in vitro and in vivo drug studies. Combining FUS-BBBD with compounds targeting microglia and tumor-associated macrophages potentially reverts the ‘immuno-cold’ tumor immune micro-environment towards an ‘immuno-hot’ state and might enhance systemic immunotherapies such as immune checkpoint inhibitor and CAR-T cell approaches. Furthermore, recent preclinical research evidenced that FUS-BBBD is able to enhance liquid biopsies by increasing the concentration of circulating biomarkers in blood. It could therefore be used for longitudinal monitoring of site-specific chemoresistance development during therapy. This presentation will provide an overview on preclinical and clinical developments in the field of FUS-BBBD-enhanced drug delivery, immune modulation and liquid biopsies. International collaboration in (pre)clinical studies with FUS-BBBD is needed to bring the field forward.
Low-risk meningioma: Initial outcomes from NRG Oncology/RTOG 0539
Authors: Rogers C Leland , Pugh Stephanie L , Vogelbaum Michael A , Perry Arie , Ashby Lynn S , Modi Jignesh M , Alleman Anthony M , Barani Igor J , Braunstein Steve , Bovi Joseph A , de Groot John F , Whitton Anthony C , Lindhorst Scott M , Deb Nimisha , Shrieve Dennis C , Shu Hui-Kuo , Bloom Beatrice , Machtay Mitchell , Mishra Mark V , Robinson Clifford G , Won Minhee , Mehta Minesh P 
Published: June 2022

Abstract

Background
Three- and five-year progression-free survival (PFS) for low-risk meningioma managed with surgery and observation reportedly exceeds 90%. Herewith we summarize outcomes for low-risk meningioma patients enrolled on NRG/RTOG 0539.

Methods
This phase II trial allocated patients to one of three groups per World Health Organization grade, recurrence status, and resection extent. Low-risk patients had either gross total (GTR) or subtotal resection (STR) for a newly diagnosed grade 1 meningioma and were observed after surgery. The primary endpoint was 3-year PFS. Adverse events (AEs) were scored using Common Terminology Criteria for Adverse Events (CTCAE) version 3.

Results
Among 60 evaluable patients, the median follow-up was 9.1 years. The 3-, 5-, and 10-year rates were 91.4% (95% CI, 84.2 to 98.6), 89.4% (95% CI, 81.3 to 97.5), 85.0% (95% CI, 75.3 to 94.7) for PFS and 98.3% (95% CI, 94.9 to 100), 98.3%, (95% CI, 94.9 to 100), 93.8% (95% CI, 87.0 to 100) for overall survival (OS), respectively. With centrally confirmed GTR, 3/5/10y PFS and OS rates were 94.3/94.3/87.6% and 97.1/97.1/90.4%. With STR, 3/5/10y PFS rates were 83.1/72.7/72.7% and 10y OS 100%. Five patients reported one grade 3, four grade 2, and five grade 1 AEs. There were no grade 4 or 5 AEs.

Conclusions
These results prospectively validate high PFS and OS for low-risk meningioma managed surgically but raise questions regarding optimal management following STR, a subcohort that could potentially benefit from adjuvant therapy.
A CRISPR/Cas12a-empowered surface plasmon resonance platform for rapid and specific diagnosis of the Omicron variant of SARS-CoV-2
Authors: Chen Zhi , Li Jingfeng , Li Tianzhong , Fan Taojian , Meng Changle , Li Chaozhou , Kang Jianlong , Chai Luxiao , Hao Yabin , Tang Yuxuan , Al-Hartomy Omar A , Wageh Swelm , Al-Sehemi Abdullah G , Luo Zhiguang , Yu Jiangtian , Shao Yonghong , Li Defa , Feng Shuai , Liu William J , He Yaqing , Ma Xiaopeng , Xie Zhongjian , Zhang Han 
Published: June 2022

Abstract
The outbreak of the COVID-19 pandemic was partially due to the challenge of identifying asymptomatic and presymptomatic carriers of the virus, and thus highlights a strong motivation for diagnostics with high sensitivity that can be rapidly deployed. On the other hand, several concerning SARS-CoV-2 variants, including Omicron, are required to be identified as soon as the samples are identified as ‘positive’. Unfortunately, a traditional PCR test does not allow their specific identification. Herein, for the first time, we have developed MOPCS (Methodologies of Photonic CRISPR Sensing), which combines an optical sensing technology-surface plasmon resonance (SPR) with the ‘gene scissors’ clustered regularly interspaced short palindromic repeat (CRISPR) technique to achieve both high sensitivity and specificity when it comes to measurement of viral variants. MOPCS is a low-cost, CRISPR/Cas12a-system-empowered SPR gene-detecting platform that can analyze viral RNA, without the need for amplification, within 38 min from sample input to results output, and achieve a limit of detection of 15 fM. MOPCS achieves a highly sensitive analysis of SARS-CoV-2, and mutations appear in variants B.1.617.2 (Delta), B.1.1.529 (Omicron) and BA.1 (a subtype of Omicron). This platform was also used to analyze some recently collected patient samples from a local outbreak in China, identified by the Centers for Disease Control and Prevention. This innovative CRISPR-empowered SPR platform will further contribute to the fast, sensitive and accurate detection of target nucleic acid sequences with single-base mutations.
High within-clutch repeatability of eggshell phenotype in Barn Swallows despite less maculated last-laid eggs
Authors: Beech Ava-Rose F , Santos Mattheus C , Smith Emily B , Berejka Ben W , Liu Yujie , Tsunekage Toshi , Levin Iris I 
Published: June 2022

Abstract
Ecological and life-history variation and both interspecific and intraspecific brood parasitism contribute to diversity in egg phenotype within the same species. In this study, Barn Swallows (Hirundo rustica erythrogaster) laid eggs with high intraclutch repeatability in egg size, shape, and maculation. Despite this high intraclutch repeatability, last-laid eggs had consistently less of the eggshell covered in spots and fewer spots than earlier-laid eggs in the clutch. We examined sources of interclutch and intraclutch variation using both direct measurements and custom software (SpotEgg, NaturePatternMatch) that provide detailed information on egg characteristics, especially maculation measures. In addition to our main findings, maculation on different sides of the egg was highly repeatable; however, only shape, proportion of the eggshell maculated, and average spot size were repeatable between first and replacement clutches. Low intraclutch variation in maculation could allow females to recognize their clutch and this may be adaptive for colonial nesting species, such as the Barn Swallow. Characterizing intraspecific variation in egg size, shape, and maculation is the first step in understanding whether intraclutch variation is low enough—and interclutch variation high enough—such that eggs could serve as identity signals.
Neural Correlates of Smooth Pursuit Eye Movements in Schizotypy and Recent Onset Psychosis: A Multivariate Pattern Classification Approach
Authors: Schröder Rebekka , Faiola Eliana , Fernanda Urquijo Maria , Bey Katharina , Meyhöfer Inga , Steffens Maria , Kasparbauer Anna-Maria , Ruef Anne , Högenauer Hanna , Hurlemann René , Kambeitz Joseph , Philipsen Alexandra , Wagner Michael , Koutsouleris Nikolaos , Ettinger Ulrich 
Published: June 2022

AbstractSchizotypy refers to a set of personality traits that bear resemblance, at subclinical level, to psychosis. Despite evidence of similarity at multiple levels of analysis, direct comparisons of schizotypy and clinical psychotic disorders are rare. Therefore, we used functional magnetic resonance imaging (fMRI) to examine the neural correlates and task-based functional connectivity (psychophysiological interactions; PPI) of smooth pursuit eye movements (SPEM) in patients with recent onset psychosis (ROP; n = 34), participants with high levels of negative (HNS; n = 46) or positive (HPS; n = 41) schizotypal traits, and low-schizotypy control participants (LS; n = 61) using machine-learning. Despite strong previous evidence that SPEM is a highly reliable marker of psychosis, patients and controls could not be significantly distinguished based on SPEM performance or blood oxygen level dependent (BOLD) signal during SPEM. Classification was, however, significant for the right frontal eye field (FEF) seed region in the PPI analyses but not for seed regions in other key areas of the SPEM network. Applying the right FEF classifier to the schizotypal samples yielded decision scores between the LS and ROP groups, suggesting similarities and dissimilarities of the HNS and HPS samples with the LS and ROP groups. The very small difference between groups is inconsistent with previous studies that showed significant differences between patients with ROP and controls in both SPEM performance and underlying neural mechanisms with large effect sizes. As the current study had sufficient power to detect such differences, other reasons are discussed.
Public attitude toward Covid‐19 vaccination: The influence of education, partisanship, biological literacy, and coronavirus understanding
Authors: Miller Jon D. , Ackerman Mark S. , Laspra Belén , Polino Carmelo , Huffaker Jordan S. 
Published: June 2022

AbstractThe Covid‐19 pandemic posed new issues about vaccination and contagious diseases that had not been the focus of public policy debate in the United States since the tuberculosis pandemic of the late 19th century and the early 20th century. Using a national address‐based probability sample of American adults in 2020 and a structural equation model, this analysis seeks to understand the role of education, age, gender, race, education, partisanship, religious fundamentalism, biological literacy, and understanding of the coronavirus to predict individual intention concerning taking the Covid‐19 vaccine. Given the substantial changes in the United States since the tuberculosis pandemic, it is important to understand the factors that drive acceptance and hesitancy about Covid‐19 vaccination. We find that education, biological literacy, and understanding of the coronavirus were strong positive predictors of willingness to be vaccinated and religious fundamentalism and conservative partisanship were strong negative predictors of intent to vaccinate. These results should be encouraging to the scientific community.
Efficacy of Inspiratory Muscle Training on Respiratory Muscle Strength in Hematopoietic Stem Cell Recipients: A Systematic Review and Meta-analysis
Authors: Sampaio Larissa Melo , Fuzari Helen Kerlen Bastos 
Published: June 2022

Objective:
To investigate whether inspiratory muscle training improves respiratory muscle strength and function and reduces dyspnea and fatigue in hematopoietic stem cell recipients.

Design:
A systematic review and meta-analysis of randomized controlled trials.

Participants:
People with hematological neoplasms who underwent hematopoietic stem cell transplantation.

Intervention:
Inspiratory muscle training with POWER breath Plus, POWERbreathe, Classic, and Threshold devices, with a load of 40% of the maximum inspiratory pressure.

Outcome Measures:
The primary outcomes were maximal inspiratory pressure, maximal expiratory pressure, forced expiratory volume in the first second of expiration (FEV1), forced vital capacity (FVC), and the FEV1/FVC ratio. Secondary outcomes were dyspnea, fatigue, respiratory rate, peripheral O2 saturation, quality of life, and functional capacity.

Results:
The search identified 3 eligible studies with a sample of 108 participants. Maximal inspiratory pressure was higher in the intervention group in the 3 studies reviewed, with an average difference of −9.3 cm H2O, −31.94 cm H2O, and −16 cm H2O in relation to the control group after inspiratory muscle training. One study found an improvement in the distance covered in the 6-minute walk test (34.22 m) and in the distance covered in the modified incremental shuttle walking test (66.43 m) in the intervention group.

Limitation:
This systematic review includes only 3 randomized controlled clinical trials.

Conclusion:
Inspiratory muscle training is effective in increasing inspiratory muscle strength and functional capacity in bone marrow transplant recipients. However, its effects on fatigue and dyspnea remain uncertain.
Comparison of Ocular Biometric Parameters Between Hispanic and Non-Hispanic Ethnicities in White Adults Undergoing Cataract Surgery
Authors: Lam Brandon C. , Weiss Menachem , Jing Frank , Zhu Christopher , Johnson Daniel A. , Kheirkhah Ahmad 
Published: June 2022

Objectives:
To compare ocular biometric parameters between Hispanic and non-Hispanic White adult patients undergoing cataract surgery.

Methods:
We included 433 adult patients undergoing surgery for senile cataract. Only patients with race and ethnicities of Hispanic and non-Hispanic White were included. The following parameters measured by the IOLMaster 700 were compared between Hispanic and non-Hispanic patients: mean keratometry, corneal astigmatism, anterior chamber depth (ACD), lens thickness, vitreous length, axial length, white-to-white diameter, and emmetropic intraocular lens power.

Results:
There were 219 Hispanic patients and 214 non-Hispanic patients with a mean age of 70.1±7.7 years (range, 50–88 years), and 66.7% were women. Although sex distribution was similar between the two groups, Hispanic patients had a lower age compared with non-Hispanic patients (69.3±8.3 vs. 70.9±6.9 years, P=0.02). In biometric values, ACD was significantly lower in Hispanic patients (3.07±0.40 mm) than in non-Hispanic patients (3.16±0.37 mm, P=0.01). Such statistically significant difference persisted after adjustment for age and sex (P=0.01). No other significant differences were found in other ocular parameters measured.

Conclusions:
Anterior chamber depth is significantly shorter in Hispanic patients compared with non-Hispanic patients. Such ethnic difference should be considered when performing cataract and corneal surgeries because this ethnic difference may be associated with a higher risk of corneal endothelial injury.
High Levels of Pretreatment HIV-1 Drug Resistance Mutations Among South African Women Who Acquired HIV During a Prospective Study
Authors: Beesham Ivana , Parikh Urvi M. , Mellors John W. , Joseph Davey Dvora L. , Heffron Renee , Palanee-Phillips Thesla , Bosman Shannon L. , Beksinska Mags , Smit Jennifer , Ahmed Khatija , Makkan Heeran , Selepe Pearl , Louw Cheryl , Kotze Philip , Hofmeyr G. Justus , Singata‐Madliki Mandisa , Rees Helen , Baeten Jared M. , Wallis Carole 
Published: June 2022

Background:
Pretreatment HIV drug resistance (PDR) undermines individual treatment success and threatens the achievement of UNAIDS 95-95-95 targets. In many African countries, limited data are available on PDR as detection of recent HIV infection is uncommon and access to resistance testing is limited. We describe the prevalence of PDR among South African women with recent HIV infection from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial.

Methods:
HIV-uninfected, sexually active women, aged 18–35 years, and seeking contraception were enrolled in the ECHO Trial at sites in South Africa, from 2015 to 2018. HIV testing was done at trial entry and repeated quarterly. We tested stored plasma samples collected at HIV diagnosis from women who seroconverted during follow-up and had a viral load >1000 copies/mL for antiretroviral resistant mutations using a validated laboratory-developed population genotyping assay, which sequences the full protease and reverse transcriptase regions. Mutation profiles were determined using the Stanford Drug Resistance Database.

Results:
We sequenced 275 samples. The median age was 23 years, and majority (98.9%, n = 272) were infected with HIV-1 subtype C. The prevalence of surveillance drug resistance mutations (SDRMs) was 13.5% (n = 37). Nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations were found in 12.4% of women (n = 34). Few women had NRTI (1.8%, n = 5) and protease inhibitor (1.1%, n = 3) mutations. Five women had multiple NRTI and NNRTI SDRMs.

Conclusions:
The high levels of PDR, particularly to NNRTIs, strongly support the recent change to the South African national HIV treatment guidelines to transition to a first-line drug regimen that excludes NNRTIs.