bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity of PD-1 blockade with nivolumab among patients with recurrent atypical/anaplastic meningioma: phase II trial results
Authors: Bi Wenya Linda , Nayak Lakshmi , Meredith David M , Driver Joseph , Du Ziming , Hoffman Samantha , Li Yvonne , Lee Eudocia Quant , Beroukhim Rameen , Rinne Mikael , McFaline-Figueroa Ricardo , Chukwueke Ugonma , McCluskey Christine , Gaffey Sarah , Cherniack Andrew D , Stefanik Jennifer , Doherty Lisa , Taubert Christina , Cifrino Meghan , LaFrankie Deborah , Graillon Thomas , Wen Patrick Y , Ligon Keith L , Al-Mefty Ossama , Huang Raymond Y , Muzikansky Alona , Chiocca E Antonio , Santagata Sandro , Dunn Ian F , Reardon David A 
Published: May 2021

Abstract

Background
Programmed death ligand 1 (PD-L1) contributes to tumor immunosuppression and is upregulated in aggressive meningiomas. We performed a phase II study of nivolumab, a programmed death 1 (PD-1) blocking antibody among patients with grade ≥2 meningioma that recurred after surgery and radiation therapy.

Methods
Twenty-five patients received nivolumab (240 mg biweekly) until progression, voluntary withdrawal, unacceptable toxicity, or death. Tumor mutational burden (TMB) and quantification of tumor-infiltrating lymphocytes (TIL) were evaluated as potential immunocorrelative biomarkers. Change in neurologic function was prospectively assessed using the Neurologic Assessment in Neuro-Oncology (NANO) scale.

Results
Enrolled patients had multiple recurrences including ≥3 prior surgeries and ≥2 prior courses of radiation in 60% and 72%, respectively. Nivolumab was well tolerated with no unexpected adverse events. Six-month progression-free survival (PFS-6) rate was 42.4% (95% CI: 22.8, 60.7) and the median OS was 30.9 months (95% CI: 17.6, NA). One patient achieved radiographic response (ongoing at 4.5 years). TMB was &gt;10/Mb in 2 of 15 profiled tumors (13.3%). Baseline TIL density was low but increased posttreatment in 3 patients including both patients with elevated TMB. Most patients who achieved PFS-6 maintained neurologic function prior to progression as assessed by NANO.

Conclusion
Nivolumab was well tolerated but failed to improve PFS-6, although a subset of patients appeared to derive benefit. Low levels of TMB and TIL density were typically observed. NANO assessment of neurologic function contributed to outcome assessment. Future studies may consider rationally designed combinatorial regimens.
Note on a description of a perfect fluid by the Kalb–Ramond field
Authors: Matsuo Yutaka , Sugamoto Akio 
Published: May 2021

Abstract
We explore a formulation of a perfect fluid in $3+1$ dimensions in terms of the Kalb–Ramond field. This was proposed long ago by Nambu and one of the present authors. In this note, we refine the statements in a more explicit form. We also comment on the duality with the Gross–Pitaevsky formulation written by a complex scalar field.
Students’ perceptions of mathematics writing and its impact on their enjoyment and self-confidence
Authors: Kaur Tandeep , Prendergast Mark 
Published: May 2021

Abstract
There have been universal endorsements of the benefits of writing as an effective medium of communicating mathematically. Writing and learning are seen as isomorphic to each other and writing can facilitate the comprehension of mathematical thinking through intrapersonal communication. Through a short writing intervention, this study investigates students’ perceptions on the use of writing in the mathematics classroom and explores the impact of writing on students’ affective domains of self-confidence and enjoyment levels in mathematics. A mixed-methods approach was employed using a pre-test, intervention, post-test design for the study. Quantitative data were collected through a questionnaire adapted from the Attitudes Towards Mathematics Inventory ( Tapia & Marsh, 2004), which was administered before and after the intervention. An analysis of the quantitative data revealed a significant increase in students’ mean scores for both enjoyment and self-confidence. Qualitative data collected in the form of students’ reflections of the writing intervention indicated that, overall, students had a positive perception of writing as a means of communicating in the mathematics classroom.
Ketofol as an Anesthetic Agent in Patients With Isolated Moderate to Severe Traumatic Brain Injury: A Prospective, Randomized Double-blind Controlled Trial
Authors: Maheswari Neha , Panda Nidhi B. , Mahajan Shalvi , Luthra Ankur , Pattnaik Smita , Bhatia Nidhi , Karthigeyan Madhivanan , Kaloria Narender , Chauhan Rajeev , Soni Shiv , Jangra Kiran , Bhagat Hemant 
Published: May 2021

Background:
The effects of ketofol (propofol and ketamine admixture) on systemic hemodynamics and outcomes in patients undergoing emergency decompressive craniectomy for traumatic brain injury (TBI) are unknown and explored in this study.

Methods:
Fifty patients with moderate/severe TBI were randomized to receive ketofol (n=25) or propofol (n=25) for induction and maintenance of anesthesia during TBI surgery. Intraoperative hemodynamic stability was assessed by continuous measurement of mean arterial pressure (MAP) and need for rescue interventions to maintain MAP within 20% of baseline. Brain relaxation scores, serum biomarker-glial fibrillary acidic protein levels, and extended Glasgow Outcome Scale (GOSE) at 30 and 90 days after discharge were also explored.

Results:
MAP was lower and hemodynamic fluctuations more frequent in patients receiving propofol compared with those receiving ketofol (P<0.05). MAP fell >20% below baseline in 22 (88%) patients receiving propofol and in 10 (40%) receiving ketofol (P=0.001), with a greater requirement for vasopressors (80% vs. 24%, respectively; P=0.02). Intraoperative brain relaxation scores and GOSE at 30 and 90 day were similar between groups. Glial fibrillary acidic protein was lower in the ketofol group (3.31±0.43 ng/mL) as compared with the propofol (3.41±0.17 ng/mL; P=0.01) group on the third postoperative day.

Conclusion:
Compared with propofol, ketofol for induction and maintenance of anesthesia during decompressive surgery in patients with moderate/severe TBI was associated with improved hemodynamic stability, lower vasopressor requirement, and similar brain relaxation.
Brain Cancer Progression: A Retrospective Multicenter Comparison of Awake Craniotomy Versus General Anesthesia in High-grade Glioma Resection
Authors: Chowdhury Tumul , Gray Kristen , Sharma Mohit , Mau Christine , McNutt Sarah , Ryan Casey , Farou Noa , Bergquist Patrick , Caldwell Catherine , Uribe Alberto A. , Todeschini Alexandre B. , Bergese Sergio D. , Bucher Oliver , Musto Grace , Azazi Emad Al , Zadeh Gelareh , Tsang Derek S. , Mansouri Seyed A. , Kakumanu Saranya , Venkatraghavan Lashmi 
Published: May 2021

Background:
High-grade gliomas impose substantial morbidity and mortality due to rapid cancer progression and recurrence. Factors such as surgery, chemotherapy and radiotherapy remain the cornerstones for treatment of brain cancer and brain cancer research. The role of anesthetics on glioma progression is largely unknown.

Methods:
This multicenter retrospective cohort study compared patients who underwent high-grade glioma resection with minimal sedation (awake craniotomy) and those who underwent craniotomy with general anesthesia (GA). Various perioperative factors, intraoperative and postoperative complications, and adjuvant treatment regimens were recorded. The primary outcome was progression-free survival (PFS); secondary outcomes were overall survival (OS), postoperative pain score, and length of hospital stay.

Results:
A total of 891 patients were included; 79% received GA, and 21% underwent awake craniotomy. There was no difference in median PFS between awake craniotomy (0.54, 95% confidence interval [CI]: 0.45-0.65 y) and GA (0.53, 95% CI: 0.48-0.60 y) groups (hazard ratio 1.05; P<0.553). Median OS was significantly longer in the awake craniotomy (1.70, 95% CI: 1.30-2.32 y) compared with that in the GA (1.25, 95% CI: 1.15-1.37 y) group (hazard ratio 0.76; P<0.009) but this effect did not persist after controlling for other variables of interest. Median length of hospital stay was significantly shorter in the awake craniotomy group (2 [range: 0 to 76], interquartile range 3 d vs. 5 [0 to 98], interquartile range 5 for awake craniotomy and GA groups, respectively; P<0.001). Pain scores were comparable between groups.

Conclusions:
There was no difference in PFS and OS between patients who underwent surgical resection of high-grade glioma with minimal sedation (awake craniotomy) or GA. Further large prospective randomized controlled studies are needed to explore the role of anesthetics on glioma progression and patient survival.
Disorders of the Fourth Cranial Nerve
Authors: Kline Lanning B. , Demer Joseph L. , Vaphiades Michael S. , Tavakoli Mehdi 
Published: May 2021

Abstract:
This review of disorders of the fourth cranial nerve includes discussion on anatomy, examination techniques, congenital and acquired etiologies, differential diagnosis, and management options. The findings of the superior oblique muscle on orbital MRI in patients with fourth nerve palsy have had a major impact on our understanding of this cranial neuropathy. In addition, briefly reviewed are rare disorders of the fourth nerve: superior oblique myokymia, Brown syndrome, and ocular neuromyotonia. It behooves the clinician to have a clear understanding of the role that the fourth cranial nerve plays in a variety of neuro-ophthalmic conditions.
Protective effects of melatonin on the white matter damage of neonatal rats by regulating NLRP3 inflammasome activity
Authors: Qin Miao , Liu Yan , Sun Mengya , Li Xianghong , Xu Jiaxin , Zhang Lulu , Jiang Hong 
Published: May 2021

Objective
The aim of the study was to investigate the protective effects and relevant mechanisms of melatonin on the white matter damage (WMD) caused by endotoxin and ischemic hypoxia in neonatal rats.

Methods
Seventy-two female neonatal rats (postnatal day 3) were randomly divided into the sham, melatonin-treated, and control groups (n = 24 for each group). The periventricular white matter was collected to evaluate the WMD and apoptosis. In addition, the reactive oxygen species (ROS) level was measured. The expression levels of nucleotide-binding domain-like receptor protein 3 (NLRP3), interleukin (IL)-1β, IL-18, pink1, parkin, Toll-like receptor (TLR)-4, and nuclear factor (NF)-κB were detected.

Results
Hematoxylin and eosin and terminal-deoxynucleoitidyl transferase mediated nick end labeling staining showed that the WMD, as well as cell degeneration, necrosis, and apoptosis in the control group, were more severe than those in the melatonin-treated group. Endotoxin and ischemic hypoxia upregulated the expression of NLRP3 and downstream inflammatory factors such as IL-1β and IL-18, which could be reversed by melatonin treatment. Melatonin increased mitochondrial autophagy marker (pink1 and parkin) expression in the white matter and reduced ROS production. Moreover, melatonin-reduced TLR4 and NF-κB expression.

Conclusions
Melatonin can inhibit the hyperactivity of NLRP3 inflammasomes by enhancing mitochondrial autophagy and inhibiting TLR4/NF-κB pathway activity. Thus, melatonin may be a promising treatment for alleviating the WMD caused by endotoxin and ischemic hypoxia in neonatal rats.
Vagus nerve stimulation affects inflammatory response and anti-apoptosis reactions via regulating miR-210 in epilepsy rat model
Authors: Bie Bizhou , Wang Zhizhong , Chen Yingchun , Sheng Liuqing , Li Huanhuan , You Huichao , Ye Jianfeng , Zhang Qing , Li Jun 
Published: May 2021

Background
Studies have shown that vagus nerve stimulation (VNS) significantly reduces the frequency of seizures. MicroRNAs (miRNAs) in cerebrospinal fluid are expected to become a new biomarker of epilepsy. Therefore, studying the interaction mechanism between the VNS and miRNAs is hopeful of bringing a new therapeutic direction for the treatment of epilepsy.

Methods
Kainic acid was used to induce the Sprague–Dawley rat epilepsy model, and the rats were treated with VNS. The miR-210 expression was determined by quantitative reverse transcription PCR (qRT-PCR). Racine score was adopted to evaluate the performance of behavioral seizures, whereas qRT-PCR and ELISA were employed to test inflammatory factors. Western blotting was implemented to testify the inflammatory and apoptotic proteins.

Results
Kainic acid-induced the Sprague–Dawley rat epilepsy model and upregulated the expression of miR-210, inflammatory response, inflammation and apoptosis-related proteins in brain tissues. In addition, compared with the epilepsy model group, miR-210 in the hippocampus of the epilepsy model rats treated with VNS was downregulated, and the expression of apoptosis-related proteins and inflammatory factors was reduced. Moreover, after further inhibiting the expression of miR-210, the inhibition of VNS on epilepsy, inflammation and apoptosis were significantly enhanced.

Summary
VNS relieves the inflammatory response and apoptosis of epileptic rats via inhibiting miR-210.
Bicentric evaluation of stabilizing sampling tubes for assessment of monocyte HLA-DR expression in clinical samples
Authors: Hamada Sarah , Jeannet Robin , Gossez Morgane , Cour Martin , Argaud Laurent , Francois Bruno , Daix Thomas , Venet Fabienne , Monneret Guillaume 
Published: May 2021

AbstractBackgroundDiminished expression of human leukocyte antigen DR on circulating monocytes (mHLA-DR), measured by standardized flow cytometry procedure, is a reliable indicator of immunosuppression in severely injured intensive care unit patients. As such, it is used as stratification criteria in clinical trials evaluating novel immunostimulating therapies. Pre-analytical constraints relative to the short delay between blood sampling and flow cytometry staining have nevertheless limited its use in multicentric studies. The objective of the present work was to compare mHLA-DR expression between whole blood samples simultaneously drawn in EDTA or Cyto-Chex® BCT tubes.MethodsIn 2 university hospitals, mHLA-DR was assessed in fresh whole blood from septic patients (n = 12) and healthy donors (n = 6) simultaneously sampled on EDTA and Cyto-Chex® BCT tubes. Staining was performed immediately after sampling and after blood storage at room temperature.ResultsWe observed the remarkable stability of mHLA-DR results when blood was collected in Cyto-Chex® BCT tubes (until 48-72 h). On baseline values, despite good correlation between tubes (r = 0.98, p< 0.001), mHLA-DR expression was systematically lower with Cyto-Chex® BCT.ConclusionThe present reports confirms the great potential of Cyto-Chex® BCT tubes to delay mHLA-DR staining in centers without rapid access to flow cytometry facilities. However, a 30 % gap exists between results obtained with EDTA and Cyto-Chex® BCT tubes. As current thresholds for clinical decisions were obtained with EDTA samples, further studies are needed to confirm clinical thresholds with Cyto-Chex® BCT tubes.
Therapeutic Anticoagulation in Non-Critically Ill Patients with Covid-19
Authors:   The ATTACC, ACTIV-4a, and REMAP-CAP Investigators, Lawler Patrick R. , Goligher Ewan C. , Berger Jeffrey S. , Neal Matthew D. , McVerry Bryan J. , Nicolau Jose C. , Gong Michelle N. , Carrier Marc , Rosenson Robert S. , Reynolds Harmony R. , Turgeon Alexis F. , Escobedo Jorge , Huang David T. , Bradbury Charlotte Ann , Houston Brett L. , Kornblith Lucy Z. , Kumar Anand , Kahn Susan R. , Cushman Mary , McQuilten Zoe , Slutsky Arthur S. , Kim Keri S. , Gordon Anthony C. , Kirwan Bridget-Anne , Brooks Maria M. , Higgins Alisa M. , Lewis Roger J. , Lorenzi Elizabeth , Berry Scott M. , Berry Lindsay R. , Angus Derek C. , McArthur Colin J. , Webb Steven A. , Farkouh Michael E. , Hochman Judith S. , Zarychanski Ryan 
Published: May 2021

AbstractBackgroundThrombo-inflammation may contribute to morbidity and mortality in Covid-19. We hypothesized that therapeutic-dose anticoagulation may improve outcomes in non-critically ill patients hospitalized for Covid-19.MethodsIn an open-label adaptive multiplatform randomized controlled trial, non-critically ill patients hospitalized for Covid-19, defined by the absence of critical care-level organ support at enrollment, were randomized to a pragmatic strategy of therapeutic-dose anticoagulation with heparin or usual care pharmacological thromboprophylaxis. The primary outcome combined survival to hospital discharge and days free of organ support through 21 days, which was evaluated with Bayesian statistical models according to baseline D-dimer.ResultsThe trial was stopped when prespecified criteria for superiority were met for therapeutic-dose anticoagulation in groups defined by high (≥2-fold elevated) and low (<2-fold elevated) D-dimer. Among 2219 participants in the final analysis, the probability that therapeutic anticoagulation increased organ support-free days compared to thromboprophylaxis was 99.0% (adjusted odds ratio 1.29, 95% credible interval 1.04 to 1.61). The adjusted absolute increase in survival to hospital discharge without organ support with therapeutic-dose anticoagulation was 4.6% (95% credible interval 0.7 to 8.1). In the primary adaptive stopping groups, the final probabilities of superiority for therapeutic anticoagulation were 97.3% in the high D-dimer group and 92.9% in the low D-dimer group. Major bleeding occurred in 1.9% and 0.9% of participants randomized to therapeutic anticoagulation and thromboprophylaxis, respectively.ConclusionsIn non-critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increases the probability of survival to hospital discharge with reduced use of organ support.Trial registration numbers: NCT02735707, NCT04505774, NCT04359277, NCT04372589
Viral metagenomic sequencing in a cohort of international travellers returning with febrile illness
Authors: Reyes Alhena , Carbo Ellen C. , thoe Slooten Joost van Harinxma , Kraakman Margriet E.M. , Sidorov Igor A. , Claas Eric C.J. , Kroes Aloys C.M. , Visser Leo G. , de Vries Jutte J.C. 
Published: May 2021

AbstractBackgroundDiagnosis of infections in returning international travellers can be challenging because of the broad spectrum of potential infectious aetiologies potentially involved. Viral metagenomic next-generation sequencing (mNGS) has the potential to detect any virus present in a patient sample and is increasingly being used for difficult to diagnose cases. The aim of this study was to analyse the performance of mNGS for viral pathogen detection in the clinical setting of international travellers returning with febrile illness.MethodsThirty-eight serum samples from international travellers returning with febrile illness and presenting at the outpatient clinic of the Leiden University Medical Center in the Netherlands in the time period 2015-2016 were selected retrospectively. Samples were processed for viral metagenomic sequencing using a probe panel capturing all known vertebrate viruses. Bioinformatic analysis was performed using Genome Detective software for metagenomic virus detection. Metagenomic virus findings were compared with viral pathogen detection using conventional methods.ResultsIn 8 out of the 38 patients (21%), a pathogenic virus was detected by mNGS. All viral pathogens detected by conventional assays were also detected by mNGS: dengue virus (n=4 patients), Epstein-Barr virus (n=2), hepatitis B virus (n=1). In addition, mNGS resulted in additional pathogenic findings in 2 patients (5%): dengue virus (n=1), and hepatitis C virus (n=1). Non-pathogenic viruses detected were: GB virus C (n=1) and torque teno viruses (n=3). High genome coverage and depth using capture probes enabled typing of the dengue viruses detected.ConclusionsViral metagenomics has the potential to assist the detection of viral pathogens and co-infections in one step in international travellers with a febrile syndrome. Furthermore, viral enrichment by probes resulted in high genome coverage and depth which enabled dengue virus typing.
Magnetic resonance spectroscopy of anoxic brain injury after cardiac arrest
Authors: Lee Jong Woo , Sreepada Lasya , Bevers Matthew , Li Karen , Scirica Benjamin , da Silva Danuzia Santana , Henderson Galen V. , Bay Camden , Lin Alexander P 
Published: May 2021

AbstractObjectiveWe describe magnetic resonance spectroscopy (MRS) changes in comatose patients undergoing targeted temperature management (TTM) after cardiac arrest, and their relationships to relevant clinical, MRI, and EEG variables.MethodsA prospective cohort of 50 patients was studied. The primary outcome was coma recovery to follow commands. Comparison of MRS measures in the posterior cingulate gyrus, parietal white matter, basal ganglia, and brainstem were also made to 25 normative control subjects.ResultsFourteen of 50 achieved coma recovery. Compared to patients who recovered, there was a significant decrease in total N-acetyl-aspartate (NAA/Cr) and glutamate; and an increase in lactate (Lac/Cr) and glutamine in patients who did not recover, with changes most prominent in the posterior cingulate gyrus. Patients who recovered had a decrease in NAA/Cr as compared to control subjects. Coma recovery was seen in patients with a moderate decrease in NAA/Cr, but the appearance of lactate resulted in a poor outcome. NAA/Cr had a linear relationship with MRI cortical apparent diffusion coefficient (ADC); lactate level exponentially increased with decreasing ADC. EEG suppression/burst suppression was universally associated with lactate elevation.ConclusionsNAA and lactate changes are associated with clinical/MRI/EEG changes consistent with anoxic brain injury and are most prominent in the posterior cingulate gyrus. NAA/Cr decrease observed in patients with good outcomes suggests mild anoxic injury in patients asymptomatic at hospital discharge. The appearance of cortical lactate represents a deterioration of aerobic energy metabolism and is associated with EEG background suppression, synaptic transmission failure, and severe, potentially irreversible anoxic injury.