bluuebunny/crossref_metadata_2025_split huggingface dataset:
MR-guided focused ultrasound liquid biopsy enriches circulating biomarkers in patients with brain tumors
Authors: Meng Ying , Pople Christopher B , Suppiah Suganth , Llinas Maheleth , Huang Yuexi , Sahgal Arjun , Perry James , Keith Julia , Davidson Benjamin , Hamani Clement , Amemiya Yutaka , Seth Arun , Leong Hon , Heyn Chinthaka C , Aubert Isabelle , Hynynen Kullervo , Lipsman Nir 
Published: March 2021

Abstract

Background
Liquid biopsy is promising for early detection, monitoring of response, and recurrence of cancer. The blood-brain barrier (BBB) limits the shedding of biomarker, such as cell-free DNA (cfDNA), into the blood from brain tumors, and their detection by conventional assays. Transcranial MR-guided focused ultrasound (MRgFUS) can safely and transiently open the BBB, providing an opportunity for less-invasive access to brain pathology. We hypothesized that MRgFUS can enrich the signal of circulating brain-derived biomarkers to aid in liquid biopsy.

Methods
Nine patients were treated in a prospective single-arm, open-label trial to investigate serial MRgFUS and adjuvant temozolomide combination in patients with glioblastoma (NCT03616860). Blood samples were collected as an exploratory measure within the hours before and after sonication, with control samples from non-brain tumor patients undergoing BBB opening (BBBO) alone (NCT03739905).

Results
Brain regions averaging 7.8 ± 6.0 cm3 (range 0.8-23.1 cm3) were successfully treated within 111 ± 39 minutes without any serious adverse events. We found MRgFUS acutely enhanced plasma cfDNA (2.6 ± 1.2-fold, P &lt; .01, Wilcoxon signed-rank test), neuron-derived extracellular vesicles (3.2 ± 1.9-fold, P &lt; .01), and brain-specific protein S100b (1.4 ± 0.2-fold, P &lt; .01). Further comparison of the cfDNA methylation profiles suggests a signature that is disease- and post-BBBO-specific, in keeping with our hypothesis. We also found cfDNA-mutant copies of isocitrate dehydrogenase 1 (IDH1) increased, although this was in only one patient known to harbor the tumor mutation.

Conclusions
This first-in-human proof-of-concept study shows MRgFUS enriches the signal of circulating brain-derived biomarkers, demonstrating the potential of the technology to support liquid biopsy for the brain.
Development of Integrated 3-Dimensional Computer Graphics Human Head Model
Authors: Kiyofuji Satoshi , Kin Taichi , Kakizawa Yukinari , Doke Takehito , Masuda Taisuke , Yamashita Juli , Shono Naoyuki , Nakatomi Hirofumi , Morita Akio , Harada Kanako , Saito Nobuhito 
Published: March 2021

Abstract

BACKGROUND
Understanding the complex anatomy of neurostructures is very important in various stages of medical education, from medical students to experienced neurosurgeons, and, ultimately, for the knowledge of human beings.

OBJECTIVE
To develop an interactive computer graphics (CG) anatomic head model and present the current progress.

METHODS
Based on the prior head 3-dimensional CG (3DCG) polygon model, 23 additional published papers and textbooks were consulted, and 2 neurosurgeons and 1 CG technician performed revision and additional polygon modeling. Three independent neurosurgeons scored the clear visibility of anatomic structures relevant to neurosurgical procedures (anterior petrosal and supracerebellar infratentorial approaches) in the integrated 3DCG model (i model) and patients’ radiological images (PRIs) such as those obtained from computed tomography, magnetic resonance imaging, and angiography.

RESULTS
The i model consisted of 1155 parts (.stl format), with a total of 313 763 375 polygons, including 10 times more information than the foundation model. The i model was able to illustrate complex and minute neuroanatomic structures that PRIs could not as well as extracranial structures such as paranasal sinuses. Our subjective analysis showed that the i model had better clear visibility scores than PRIs, particularly in minute nerves, vasculatures, and dural structures.

CONCLUSION
The i model more clearly illustrates minute anatomic structures than PRIs and uniquely illustrates nuclei and fibers that radiological images do not. The i model complements cadaveric dissection by increasing accessibility according to spatial, financial, ethical, and social aspects and can contribute to future medical education.
Transsylvian Insular Glioma Surgery: New Classification System, Clinical Outcome in a Consecutive Series of 79 Cases
Authors: Pitskhelauri David , Bykanov Andrey , Konovalov Alexander , Danilov Gleb , Buklina Svetlana , Sanikidze Alexander , Sufianov Rinat 
Published: March 2021

Abstract

BACKGROUND
Surgery of insular glial tumors remains a challenge because of high incidence of postoperative neurological deterioration and the complex anatomy of the insular region.

OBJECTIVE
To explore the prognostic role of our and Berger-Sanai classifications on the extent of resection (EOR) and clinical outcome.

METHODS
From 2012 to 2017, a transsylvian removal of insular glial tumors was performed in 79 patients. The EOR was assessed depending on magnetic resonance imaging scans performed in the first 48 h after surgery.

RESULTS
The EOR ≥90% was achieved in 30 (38%) cases and <90% in 49 (62.0%) cases. In the early postoperative period, the new neurological deficit was observed in 31 (39.2%) patients, and in 5 patients (6.3%), it persisted up to 3 mo.
We proposed a classification of insular gliomas based on its volumetric and anatomical characteristics. A statistically significant differences were found between proposed classes in tumor volume before and after surgery (P < .001), EOR (P = .02), rate of epileptic seizures before the surgical treatment (P = .04), and the incidence of persistent postoperative complications (P = .03).
In the logistic regression model, tumor location in zone II (Berger-Sanai classification) was the predictor significantly related to less likely EOR of ≥90% and the maximum rate of residual tumor detection (P = .02).

CONCLUSION
The proposed classification of the insular gliomas was an independent predictor of the EOR and persistent postoperative neurological deficit. According to Berger-Sanai classification, zone II was a predictor of less EOR through the transsylvian approach.
Ascorbate–glutathione pathways mediated by cytokinin regulate H2O2 levels in light-controlled rose bud burst
Authors: Porcher Alexis , Guérin Vincent , Leduc Nathalie , Lebrec Anita , Lothier Jérémy , Vian Alain 
Published: March 2021

AbstractRosebush (Rosa “Radrazz”) plants are an excellent model to study light control of bud outgrowth since bud outgrowth only arises in the presence of light and never occurs in darkness. Recently, we demonstrated high levels of hydrogen peroxide (H2O2) present in the quiescent axillary buds strongly repress the outgrowth process. In light, the outgrowing process occurred after H2O2 scavenging through the promotion of Ascorbic acid–Glutathione (AsA–GSH)-dependent pathways and the continuous decrease in H2O2 production. Here we showed Respiratory Burst Oxidase Homologs expression decreased in buds during the outgrowth process in light. In continuous darkness, the same decrease was observed although H2O2 remained at high levels in axillary buds, as a consequence of the strong inhibition of AsA–GSH cycle and GSH synthesis preventing the outgrowth process. Cytokinin (CK) application can evoke bud outgrowth in light as well as in continuous darkness. Furthermore, CKs are the initial targets of light in the photocontrol process. We showed CK application to cultured buds in darkness decreases bud H2O2 to a level that is similar to that observed in light. Furthermore, this treatment restores GSH levels and engages bud burst. We treated plants with buthionine sulfoximine, an inhibitor of GSH synthesis, to solve the sequence of events involving H2O2/GSH metabolisms in the photocontrol process. This treatment prevented bud burst, even in the presence of CK, suggesting the sequence of actions starts with the positive CK effect on GSH that in turn stimulates H2O2 scavenging, resulting in initiation of bud outgrowth.
Independent associations of lymphopenia and neutropenia in patients with systemic lupus erythematosus: a longitudinal, multinational study
Authors: Kandane-Rathnayake Rangi , Louthrenoo Worawit , Golder Vera , Luo Shue-Fen , Wu Yeong-Jian J , Lateef Aisha , Cho Jiacai , Li Zhanguo , An Yuan , Hamijoyo Laniyati , Navarra Sandra , Zamora Leonid , Katsumata Yasuhiro , Harigai Masayoshi , Sockalingam Sargunan , Chan Madelynn , Chen Yi-Hsing , O'Neill Sean , Goldblatt Fiona , Hao Yanjie , Zhang Zhuoli , Kikuchi Jun , Takeuchi Tsutomu , Lau Chak Sing , Nikpour Mandana , Morand Eric , Hoi Alberta ,   for the Asia Pacific Lupus Collaboration
Published: March 2021

Abstract

Objective
The prevalence and associations of leucopenia in SLE remain incompletely understood. We evaluated associations of disease activity and medication use with leucopenia (lymphopenia and neutropenia) in a multinational, prospectively followed SLE cohort.

Methods
Data from the Asia Pacific Lupus Collaboration cohort, in which disease activity and medications were prospectively captured from 2013 to 2018, were used. Predictors of lymphopenia (lymphocyte count &lt;0.8 × 109/l) and neutropenia (neutrophil count &lt;1.5 × 109/l) were examined using multiple failure, time-dependent survival analyses.

Results
Data from 2330 patients and 18 287 visits were analysed. One thousand and eighteen patients (43.7%) had at least one episode of leucopenia; 867 patients (37.2%) had lymphopenia, observed in 3065 (16.8%) visits, and 292 (12.5%) patients had neutropenia, in 622 (3.4%) visits. After multivariable analyses, lymphopenia was associated with overall disease activity, ESR, serology, prednisolone, AZA, MTX, tacrolimus, CYC and rituximab use. MTX and ciclosporin were negatively associated with neutropenia. Lupus low disease activity state was negatively associated with both lymphopenia and neutropenia.

Conclusion
Both lymphopenia and neutropenia were common in SLE patients but were differentially associated with disease and treatment variables. Lymphopenia and neutropenia should be considered independently in studies in SLE.
SARS-CoV-2 transmission in intercollegiate athletics not fully mitigated with daily antigen testing
Authors: Moreno Gage K. , Braun Katarina M. , Pray Ian W. , Segaloff Hannah E. , Lim Ailam , Poulson Keith , Meiman Jonathan , Borcher James , Westergaard Ryan P. , Moll Michael K. , Friedrich Thomas C. , O’Connor David H. 
Published: March 2021

AbstractBackgroundHigh frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester despite mandatory directly observed daily antigen testing.MethodsDuring the fall 2020 semester, athletes and staff in both programs were tested daily using Quidel’s Sofia SARS Antigen Fluorescent Immunoassay (FIA), with positive antigen results requiring confirmatory testing with real-time reverse transcription polymerase chain reaction (RT-PCR). We used genomic sequencing to investigate transmission dynamics in these two outbreaks.ResultsIn Outbreak 1, 32 confirmed cases occurred within a university athletics program after the index patient attended a meeting while infectious despite a negative antigen test on the day of the meeting. Among isolates sequenced from Outbreak 1, 24 (92%) of 26 were closely related, suggesting sustained transmission following an initial introduction event. In Outbreak 2, 12 confirmed cases occurred among athletes from two university programs that faced each other in an athletic competition despite receiving negative antigen test results on the day of the competition. Sequences from both teams were closely related and unique from strains circulating in the community, suggesting transmission during intercollegiate competition.ConclusionsThese findings suggest that antigen testing alone, even when mandated and directly observed, may not be sufficient as an intervention to prevent SARS-CoV-2 outbreaks in congregate settings, and highlights the importance of supplementing serial antigen testing with appropriate mitigation strategies to prevent SARS-CoV-2 outbreak in congregate settings.SummaryHigh frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, here we describe two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester.
COVID-19-associated school closures and related efforts to sustain education and subsidized meal programs, United States, February 18–June 30, 2020
Authors: Zviedrite Nicole , Hodis Jeffrey D. , Jahan Ferdous , Gao Hongjiang , Uzicanin Amra 
Published: March 2021

AbstractPre-emptive school closures are frontline community mitigation measures recommended by CDC for implementation during severe pandemics. This study describes the spatiotemporal patterns of publicly announced school closures implemented in response to the coronavirus disease 2019 (COVID-19) pandemic and assesses how public K-12 districts adjusted their methods of education delivery and provision of subsidized meals. During February 18–June 30, 2020, we used daily systematic media searches to identify publicly announced coronavirus disease 2019 (COVID-19)–related school closures lasting ≥1 day in the United States (US). We also collected statewide school closure policies from state government websites. Data on distance learning and subsidized meal programs were collected from a stratified sample of 600 school districts. The first COVID-19–associated school closure occurred on February 27, 2020 in Washington state. By March 30, 2020, all but one US public school districts were closed, representing the first-ever nearly synchronous nationwide closure of public K-12 schools in the US. Approximately 100,000 public schools were closed for ≥8 weeks because of COVID-19, affecting >50 million K-12 students. Of 600 districts sampled, the vast majority offered distance learning (91.0%) and continued provision of subsidized meal programs (78.8%) during the closures. Despite the sudden and prolonged nature of COVID-19–associated school closures, schools demonstrated flexibility by implementing distance learning and alternate methods to continue subsidized meal programs.
A quantitative risk estimation platform for indoor aerosol transmission of COVID-19
Authors: Parhizkar Hooman , Van Den Wymelenberg Kevin , Haas Charles , Corsi Richard 
Published: March 2021

AbstractAerosol transmission has played a significant role in the transmission of COVID-19 disease worldwide. We developed a COVID-19 aerosol transmission risk estimation platform to better understand how key parameters associated with indoor spaces and infector emissions affect inhaled deposited dose of aerosol particles that convey the SARS-CoV-2 virus. The model calculates the concentration of size-resolved, virus-laden aerosol particles in well-mixed indoor air challenged by emissions from an index case(s). The model uses a mechanistic approach, accounting for particle emission dynamics, particle deposition to indoor surfaces, ventilation rate, and single-zone filtration. The novelty of this model relates to the concept of “inhaled & deposited dose” in the respiratory system of receptors linked to a dose-response curve for human coronavirus HCoV-229E. We estimated the volume of inhaled & deposited dose of particles in the 0.5 to 4 μm range expressed in picoliters (pL) in a well-documented COVID-19 outbreak in restaurant X in Guangzhou China. We anchored the attack rate with the dose-response curve of HCoV-229E which provides a preliminary estimate of the average SARS-CoV-2 dose per person, expressed in plaque forming units (PFUs). For a reasonable emission scenario, we estimate approximately three PFU per pL deposited, yielding roughly 10 PFUs deposited in the respiratory system of those infected in Restaurant X. To explore the platform’s utility, we tested the model with four COVID-19 outbreaks. The risk estimates from the model fit reasonably well with the reported number of confirmed cases given available metadata from the outbreaks and uncertainties associated with model assumptions.Practical ImplicationsThe model described in this paper is more mechanistic in nature than standard probabilistic models that fail to account for particle deposition to indoor materials, filtration, and deposition of particles in the respiratory system of receptors. As such, it provides added insights into how building-related factors affect relative infection risk associated with inhaled deposited dose. An online version of this mechanistic aerosol risk estimation platform is available at Safeairspaces.com. Importantly, the modular nature of this approach allows for easy updates when new information is available regarding dose-response relationships for SARS-CoV-2 or its variants.
Engineered Peptide-Functionalized Hydrogels Modulate the RNA Transcriptome of Human Nucleus Pulposus Cells In Vitro
Authors: Barcellona Marcos N. , Speer Julie E. , Jing Liufang , Gupta Munish C. , Buchowski Jacob M. , Kelly Michael P. , Setton Lori A. 
Published: March 2021

AbstractDegeneration and aging of the nucleus pulposus (NP) of the intervertebral disc (IVD) is accompanied by alterations in NP cell phenotype marked by a shift towards a fibroblast-like, catabolic state. We have recently demonstrated an ability to manipulate the phenotype of human adult degenerative NP cells through 2D culture upon poly(ethylene glycol) (PEG) based hydrogels dually functionalized with integrin- and syndecan-binding laminin-mimetic peptides (LMPs). In the present study, we sought to understand the transcriptomic changes elicited through NP cell interactions with the LMP-functionalized hydrogel system (LMP gel) by examining targets of interesta prioriand by conducting unbiased analysis to identify novel mechanosensitive targets. The results of gene specific analysis demonstrated that the LMP gel promoted adult degenerative NP cells to upregulate 148 genes including several NP markers (e.g. NOG and ITGA6) and downregulate 277 genes, namely several known fibroblastic markers. Additionally, 13 genes associated with G protein-coupled receptors, many of which are known drug targets, were identified as differentially regulated following culture upon the gel. Furthermore, through gene set enrichment analysis we identified over 700 pathways enriched amongst the up- and downregulated genes including pathways related to cell differentiation, notochord morphogenesis, and intracellular signaling. Together these findings demonstrate the global mechanobiological effects induced by the LMP gel and confirm the ability of this substrate to modulate NP cell phenotype.
Multiple classes of bactericidal antibiotics cause DNA double strand breaks inStaphylococcus aureus
Authors: Clarke Rebecca S. , Ha Kam Pou , Edwards Andrew M. 
Published: March 2021

AbstractAntibiotics inhibit essential bacterial processes, resulting in arrest of growth and in some cases cell death. Many antibiotics are also reported to trigger endogenous production of reactive oxygen species (ROS), which damage DNA and other macromolecules. However, the type of DNA damage that arises and the mechanisms used by bacteria to repair it are largely unclear. We found that several different classes of antibiotic triggered dose-dependent DNA damage inStaphylococcus aureus, including some bacteriostatic drugs. Damage was heterogenous and varied in magnitude between strains. However, antibiotic-triggered DNA damage led to double strand breaks, the processing of which by the RexAB helicase/nuclease complex triggered the SOS response and reduced staphylococcal susceptibility to most of the antibacterials tested. In most cases, DNA DSBs occurred under aerobic but not anaerobic conditions, suggesting a role for ROS. We conclude that DNA double strand breaks are a common occurrence during bacterial exposure to several different antibiotic classes and that repair of this damage by the RexAB complex promotes bacterial survival.
HOXA9acts as a regulatory switch in acute myeloid leukaemia and myeloproliferative neoplasms
Authors: Talarmain Laure , Clarke Matthew A. , Shorthouse David , Fisher Jasmin , Hall Benjamin A 
Published: March 2021

AbstractBlood malignancies arise from the dysregulation of haematopoiesis. The type of blood cell and the specific order of oncogenic events initiating abnormal growth ultimately determine the cancer subtype and subsequent clinical outcome. HOXA9 plays an important role in acute myeloid leukaemia (AML) prognosis by promoting blood cell expansion and altering differentiation; however, the function of HOXA9 in other blood malignancies is still unclear. Here, we demonstrate the importance of this gene in chronic myeloproliferative neoplasms (MPN) and highlight the biological switch and prognosis marker properties of HOXA9 in AML and MPN. This binary switch function can explain the clinical stratification of these two blood disorders. First, we establish the ability of HOXA9 to stratify AML patients with distinct cellular and clinical outcomes. Then, through the use of a computational network model of MPN, we show that the self-activation of HOXA9 and its relationship to JAK2 and TET2 can explain the branching progression of JAK2/TET2 mutant MPN patients towards divergent clinical characteristics. Finally, we predict a connection between the RUNX1 and MYB genes and a suppressive role for the NOTCH pathway in MPN diseases.
Fungal taste for minerals: the ectomycorrhizal fungusPaxillus involutustriggers specific genes when extracting potassium from different silicates
Authors: Pinzari F. , Jungblut A.D. , Cuadros J. 
Published: March 2021

AbstractSilicates make up about 90% of the Earth’s crust and constitute the main source of mineral nutrients for microorganisms and plants. Fungi can actively weather silicates to extract nutrients. However, it is unclear whether they are able to obtain the same amounts of nutrients and use the same mechanisms when tapping into different mineral sources. We performed a microcosm experiment using the ectomycorrhizal basidiomycetesPaxillus involutusand the silicates K-vermiculite, muscovite and phlogopite as only potassium sources, as they show a different resistance for the removal of K cations from the mineral structure. A combination of transcriptomic, elemental and SEM analyses showed that different minerals stimulated specific weathering mechanisms and led to a change in fungal genes expression. The differential expression of the fungal genes generated alternative chemical attacks on the minerals, resulting in a tailored dissolution and selective uptake of chemical elements according to the leachability of K from the silicate mineral. The K uptake capacity of the fungus was highest with vermiculite in comparison to growth on phlogopite and muscovite. The findings provide new insights into fungal-mineral interactions that will help to interpret key processes for the homeostasis of soil environments.