tbuckley/cabot-search huggingface dataset:
The BCI Glossary: a first proposal for a community review
Authors: Alberto Antonietti, Pradeep Balachandran, Ali Hossaini, Yaoping Hu, Davide Valeriani
Journal: Brain-Computer Interfaces (2021)

The description of Brain-Computer Interfaces (BCI) can lead to confusion because of the high heterogeneity of devices, protocols, and applications. Besides, different professional categories are involved: end-users, clinicians, therapists, and engineers; each one having different conceptions of BCI-related terms. This can cause misunderstandings and errors, and it makes it impossible to compare different systems and their performances. The IEEE P2731 working group has been working on a standardized glossary for BCI research, together with a functional model for BCI. Here, we are presenting a first version of the BCI glossary, generated by the collective effort of the working group. One hundred fifty-three terms have been identified to be critical for describing in a standardized way BCI systems and their related aspects (e.g., the neurophysiological characteristics of the neural signals recorded). Each term has been provided with a definition, merged from multiple ones proposed by working group members, with appropriate references to the current state of the art. Finally, we are asking for feedback and suggestions about this first version of the BCI glossary to the wider community of BCI users and researchers. External inputs will improve the glossary, which will become, after further revisions, an official IEEE standard.
Heterologous prime-boost vaccination targeting MAGE-type antigens promotes tumor T-cell infiltration and improves checkpoint blockade therapy
Authors: James McAuliffe, Hok Fung Chan, Laurine Noblecourt, Ramiro Andrei Ramirez-Valdez, Vinnycius Pereira-Almeida, Yaxuan Zhou, Emily Pollock, Federica Cappuccini, Irina Redchenko, Adrian VS Hill, Carol Sze Ki Leung, Benoit J Van den Eynde
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background The clinical benefit of immune checkpoint blockade (ICB) therapy is often limited by the lack of pre-existing CD8 + T cells infiltrating the tumor. In principle, CD8 + T-cell infiltration could be promoted by therapeutic vaccination. However, this remains challenging given the paucity of vaccine platforms able to induce the strong cytotoxic CD8 + T-cell response required to reject tumors. A therapeutic cancer vaccine that induces a robust cytotoxic CD8 + T-cell response against shared tumor antigens and can be combined with ICB could improve the outcome of cancer immunotherapy. Methods Here, we developed a heterologous prime-boost vaccine based on a chimpanzee adenovirus (ChAdOx1) and a modified vaccinia Ankara (MVA) encoding MAGE-type antigens, which are tumor-specific shared antigens expressed in different tumor types. The mouse MAGE-type antigen P1A was used as a surrogate to study the efficacy of the vaccine in combination with ICB in murine tumor models expressing the P1A antigen. To characterize the vaccine-induced immune response, we performed flow cytometry and transcriptomic analyses. Results The ChAdOx1/MVA vaccine displayed strong immunogenicity with potent induction of CD8 + T cells. When combined with anti-Programmed Cell Death Protein 1 (PD-1), the vaccine induced superior tumor clearance and survival in murine tumor models expressing P1A compared with anti-PD-1 alone. Remarkably, ChAdOx1/MVA P1A vaccination promoted CD8 + T-cell infiltration in the tumors, and drove inflammation in the tumor microenvironment, turning ‘cold’ tumors into ‘hot’ tumors. Single-cell transcriptomic analysis of the P1A-specific CD8 + T cells revealed an expanded population of stem-like T cells in the spleen after the combination treatment as compared with vaccine alone, and a reduced PD-1 expression in the tumor CD8 + T cells. Conclusions These findings highlight the synergistic potency of ChAdOx1/MVA MAGE vaccines combined with anti-PD-1 for cancer therapy, and establish the foundation for clinical translation of this approach. A clinical trial of ChadOx1/MVA MAGE-A3/NY-ESO-1 combined with anti-PD-1 will commence shortly.
A tumor microenvironment responsive nanosystem for chemodynamic/chemical synergistic theranostics of colorectal cancer
Authors: Liying Wang, Jingya Xia, Hongjie Fan, Min Hou, Huiyang Wang, Xiaoyan Wang, Ke Zhang, Liping Cao, Xiangrui Liu, Jun Ling, Hong Yu, Xia Wu, Jihong Sun
Journal: Theranostics (2021)

Rationale: The synergism of new modalities alongside chemodynamic therapy into common chemotherapy has shown promising potential in clinical applications. This paper reports a tumor microenvironment-responsive nanosystem for chemodynamic/chemical synergistic therapy and magnetic resonance imaging (MRI). Methods: The biodegradable nanosystem is synthesized using a surface-modified chain transfer agent for surface-initiated living radical polymerization of the chemotherapeutic drug. Results: In this nanosystem, named CAMNSN@PSN38, the cycling time and solubility of the chemotherapeutic drug are improved. The nanoparticles delivered to tumor tissues gradually release the chemotherapeutic drug and Mn2+ through glutathione (GSH)-triggered biodegradation in the tumor microenvironment. SN38, the released chemotherapeutic drug, not only shows excellent chemical therapy effects but also improves the generation of H2O2. Furthermore, with the Fenton-like agent Mn2+, the generation of reactive oxygen species (ROS) is improved markedly. Finally, CAMNSN@PSN38 shows excellent inhibition of tumor growth in three colorectal cancer tumor models, with an improved accumulation of ROS and controlled release of SN38. Conclusions: The CAMNSN@PSN38-mediated chemodynamic/chemical synergistic therapy provides a promising paradigm for the treatment and MRI-guided therapy of colorectal cancer.
Outcomes in the ISCHEMIA Trial Based on Coronary Artery Disease and Ischemia Severity
Authors: Harmony R. Reynolds, Leslee J. Shaw, James K. Min, Courtney B. Page, Daniel S. Berman, Bernard R. Chaitman, Michael H. Picard, Raymond Y. Kwong, Sean M. O’Brien, Zhen Huang, Daniel B. Mark, Ranjit K. Nath, Sudhanshu K. Dwivedi, Paola E.P. Smanio, Peter H. Stone, Claes Held, Matyas Keltai, Sripal Bangalore, Jonathan D. Newman, John A. Spertus, Gregg W. Stone, David J. Maron, Judith S. Hochman
Journal: Circulation (2021)

The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) postulated that patients with stable coronary artery disease (CAD) and moderate or severe ischemia would benefit from revascularization. We investigated the relationship between severity of CAD and ischemia and trial outcomes, overall and by management strategy. In total, 5179 patients with moderate or severe ischemia were randomized to an initial invasive or conservative management strategy. Blinded, core laboratory-interpreted coronary computed tomographic angiography was used to assess anatomic eligibility for randomization. Extent and severity of CAD were classified with the modified Duke Prognostic Index (n=2475, 48%). Ischemia severity was interpreted by independent core laboratories (nuclear, echocardiography, magnetic resonance imaging, exercise tolerance testing, n=5105, 99%). We compared 4-year event rates across subgroups defined by severity of ischemia and CAD. The primary end point for this analysis was all-cause mortality. Secondary end points were myocardial infarction (MI), cardiovascular death or MI, and the trial primary end point (cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest). Relative to mild/no ischemia, neither moderate ischemia nor severe ischemia was associated with increased mortality (moderate ischemia hazard ratio [HR], 0.89 [95% CI, 0.61-1.30]; severe ischemia HR, 0.83 [95% CI, 0.57-1.21]; P=0.33). Nonfatal MI rates increased with worsening ischemia severity (HR for moderate ischemia, 1.20 [95% CI, 0.86-1.69] versus mild/no ischemia; HR for severe ischemia, 1.37 [95% CI, 0.98-1.91]; P=0.04 for trend, P=NS after adjustment for CAD). Increasing CAD severity was associated with death (HR, 2.72 [95% CI, 1.06-6.98]) and MI (HR, 3.78 [95% CI, 1.63-8.78]) for the most versus least severe CAD subgroup. Ischemia severity did not identify a subgroup with treatment benefit on mortality, MI, the trial primary end point, or cardiovascular death or MI. In the most severe CAD subgroup (n=659), the 4-year rate of cardiovascular death or MI was lower in the invasive strategy group (difference, 6.3% [95% CI, 0.2%-12.4%]), but 4-year all-cause mortality was similar. Ischemia severity was not associated with increased risk after adjustment for CAD severity. More severe CAD was associated with increased risk. Invasive management did not lower all-cause mortality at 4 years in any ischemia or CAD subgroup. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01471522.
Exploration of Proton Pump Inhibitors Use During Pregnancy and Preeclampsia
Authors: Ahhyung Choi, Yunha Noh, So-Hee Park, Seung-Ah Choe, Ju-Young Shin
Journal: JAMA Network Open (2021)

Preeclampsia affects 3% to 8% of pregnancies worldwide. Preclinical studies have suggested that proton pump inhibitors (PPIs) have preventive effects on preeclampsia1; however, studies in humans are limited and present conflicting results.2,3,4 Moreover, these studies have limitations, such as recall bias, residual confounding bias, and a lack of dosage information, which warrants additional studies to assess the association of preeclampsia and PPIs. Accordingly, we investigated whether PPI use during pregnancy is associated with the rate of preeclampsia.
Immunotherapy (Cemiplimab)-Induced Bullous Pemphigoid
Authors: Hannes Grünig, Stephan M. Skawran, Mirjam Nägeli, Jivko Kamarachev, Martin W. Huellner
Journal: Clinical Nuclear Medicine (2021)

Abstract A 78-year-old man with multiple squamous cell carcinomas of the skin underwent 18 F-FDG-PET/CT for restaging after 4 cycles of cemiplimab. The scan showed new disseminated FDG-avid skin lesions. Dermatologic examination and biopsy revealed bullous pemphigoid. Discontinuation of cemiplimab and treatment with corticosteroids led to clinical improvement, after which treatment with cemiplimab was resumed. A broad spectrum of inflammatory adverse events can occur in patients treated with immune checkpoint inhibitors, and FDG avidity of these lesions may mimic metastases. Knowledge of such imaging pitfalls is essential for interpreting 18 F-FDG-PET/CT, particularly if they occur in the same organ as the primary tumor.
Smoke health costs and the calculus for wildfires fuel management: a modelling study
Authors: Nicolas Borchers-Arriagada, David M J S Bowman, Owen Price, Andrew J Palmer, Stephanie Samson, Hamish Clarke, Gonzalo Sepulveda, Fay H Johnston
Journal: The Lancet Planetary Health (2021)

Smoke from uncontrolled wildfires and deliberately set prescribed burns has the potential to produce substantial population exposure to fine particulate matter (PM2·5). We aimed to estimate historical health costs attributable to smoke-related PM2·5 from all landscape fires combined, and the relative contributions from wildfires and prescribed burns, in New South Wales, Australia.We quantified PM2·5 from all landscape fire smoke (LFS) and estimated the attributable health burden and daily health costs between July 1, 2000, and June 30, 2020, for all of New South Wales and by smaller geographical regions. We combined these results with a spatial database of landscape fires to estimate the relative total and per hectare health costs attributable to PM2·5 from wildfire smoke (WFS) and prescribed burning smoke (PBS).We estimated health costs of AU$ 2013 million (95% CI 718-3354; calculated with the 2018 value of the AU$). $1653 million (82·1%) of costs were attributable to WFS and $361 million (17·9%) to PBS. The per hectare health cost was of $105 for all LFS days ($104 for WFS and $477 for PBS). In sensitivity analyses, the per hectare costs associated with PBS was consistently higher than for WFS under a range of different scenarios.WFS and PBS produce substantial health costs. Total health costs are higher for WFS, but per hectare costs are higher for PBS. This should be considered when assessing the trade-offs between prescribed burns and wildfires.None.
Cognitive-Behavior Therapy, Sertraline, and Their Combination for Children and Adolescents With Obsessive-Compulsive Disorder
Journal: JAMA (2004)

ContextThe empirical literature on treatment of obsessive-compulsive disorder (OCD) in children and adolescents supports the efficacy of short-term OCD-specific cognitive-behavior therapy (CBT) or medical management with selective serotonin reuptake inhibitors. However, little is known about their relative and combined efficacy.ObjectiveTo evaluate the efficacy of CBT alone and medical management with the selective serotonin reuptake inhibitor sertraline alone, or CBT and sertraline combined, as initial treatment for children and adolescents with OCD.Design, Setting, and ParticipantsThe Pediatric OCD Treatment Study, a balanced, masked randomized controlled trial conducted in 3 academic centers in the United States and enrolling a volunteer outpatient sample of 112 patients aged 7 through 17 years with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD and a Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score of 16 or higher. Patients were recruited between September 1997 and December 2002.InterventionsParticipants were randomly assigned to receive CBT alone, sertraline alone, combined CBT and sertraline, or pill placebo for 12 weeks.Main Outcome MeasuresChange in CY-BOCS score over 12 weeks as rated by an independent evaluator masked to treatment status; rate of clinical remission defined as a CY-BOCS score less than or equal to 10.ResultsNinety-seven of 112 patients (87%) completed the full 12 weeks of treatment. Intent-to-treat random regression analyses indicated a statistically significant advantage for CBT alone (P = .003), sertraline alone (P = .007), and combined treatment (P = .001) compared with placebo. Combined treatment also proved superior to CBT alone (P = .008) and to sertraline alone (P = .006), which did not differ from each other. Site differences emerged for CBT and sertraline but not for combined treatment, suggesting that combined treatment is less susceptible to setting-specific variations. The rate of clinical remission for combined treatment was 53.6% (95% confidence interval [CI], 36%-70%); for CBT alone, 39.3% (95% CI, 24%-58%); for sertraline alone, 21.4% (95% CI, 10%-40%); and for placebo, 3.6% (95% CI, 0%-19%). The remission rate for combined treatment did not differ from that for CBT alone (P = .42) but did differ from sertraline alone (P = .03) and from placebo (P&lt;.001). CBT alone did not differ from sertraline alone (P = .24) but did differ from placebo (P = .002), whereas sertraline alone did not (P = .10). The 3 active treatments proved acceptable and well tolerated, with no evidence of treatment-emergent harm to self or to others.ConclusionChildren and adolescents with OCD should begin treatment with the combination of CBT plus a selective serotonin reuptake inhibitor or CBT alone.
De novo transcriptomic subtyping of colorectal cancer liver metastases in the context of tumor heterogeneity
Authors: Seyed H. Moosavi, Peter W. Eide, Ina A. Eilertsen, Tuva H. Brunsell, Kaja C. G. Berg, Bård I. Røsok, Kristoffer W. Brudvik, Bjørn A. Bjørnbeth, Marianne G. Guren, Arild Nesbakken, Ragnhild A. Lothe, Anita Sveen
Journal: Genome Medicine (2021)

Abstract Background Gene expression-based subtyping has the potential to form a new paradigm for stratified treatment of colorectal cancer. However, current frameworks are based on the transcriptomic profiles of primary tumors, and metastatic heterogeneity is a challenge. Here we aimed to develop a de novo metastasis-oriented framework. Methods In total, 829 transcriptomic profiles from patients with colorectal cancer were analyzed, including primary tumors, liver metastases, and non-malignant liver samples. High-resolution microarray gene expression profiling was performed of 283 liver metastases from 171 patients treated by hepatic resection, including multiregional and/or multi-metastatic samples from each of 47 patients. A single randomly selected liver metastasis sample from each patient was used for unsupervised subtype discovery by nonnegative matrix factorization, and a random forest prediction model was trained to classify multi-metastatic samples, as well as liver metastases from two independent series of 308 additional patients. Results Initial comparisons with non-malignant liver samples and primary colorectal tumors showed a highly variable degree of influence from the liver microenvironment in metastases, which contributed to inter-metastatic transcriptomic heterogeneity, but did not define subtype distinctions. The de novo liver metastasis subtype (LMS) framework recapitulated the main distinction between epithelial-like and mesenchymal-like tumors, with a strong immune and stromal component only in the latter. We also identified biologically distinct epithelial-like subtypes originating from different progenitor cell types. LMS1 metastases had several transcriptomic features of cancer aggressiveness, including secretory progenitor cell origin, oncogenic addictions, and microsatellite instability in a microsatellite stable background, as well as frequent RAS / TP53 co-mutations. The poor-prognostic association of LMS1 metastases was independent of mutation status, clinicopathological variables, and current subtyping frameworks (consensus molecular subtypes and colorectal cancer intrinsic subtypes). LMS1 was also the least heterogeneous subtype in comparisons of multiple metastases per patient, and tumor heterogeneity did not confound the prognostic value of LMS1. Conclusions We report the first large study of multi-metastatic gene expression profiling of colorectal cancer. The new metastasis-oriented subtyping framework showed potential for clinically relevant transcriptomic classification in the context of metastatic heterogeneity, and an LMS1 mini-classifier was constructed to facilitate prognostic stratification and further clinical testing.
Single inhaler triple therapy (SITT) in asthma: Systematic review and practice implications
Authors: Alvar Agusti, Leonardo Fabbri, Lies Lahousse, Dave Singh, Alberto Papi
Journal: Allergy (2021)

Abstract A significant number of patients with asthma remain uncontrolled despite treatment with inhaled corticosteroids (ICS) and long‐acting β2 adrenergic bronchodilators (LABA). The addition of long‐acting antimuscarinic agents (LAMA) can improve the management of asthma in these patients. Recently, three novel triple therapy (ICS/LABA/LAMA) formulations in a single‐inhaler device (SITT) have been investigated in patients with uncontrolled asthma despite ICS/LABA treatment. Here, we review systematically the evidence available to date in relation to SITT in patients with uncontrolled asthma despite ICS‐LABA treatment and conclude that SITT is a safe and effective therapeutic alternative in these patients. We also discuss how to position this new therapeutic alternative in their practical clinical management as well as the opportunities and challenges that it may generate for patients, physicians, and payers.
Pre-therapeutic microglia activation and sex determine therapy effects of chronic immunomodulation
Authors: Gloria Biechele, Tanja Blume, Maximilian Deussing, Benedikt Zott, Yuan Shi, Xianyuan Xiang, Nicolai Franzmeier, Gernot Kleinberger, Finn Peters, Katharina Ochs, Carola Focke, Christian Sacher, Karin Wind, Claudio Schmidt, Simon Lindner, Franz-Josef Gildehaus, Florian Eckenweber, Leonie Beyer, Barbara von Ungern-Sternberg, Peter Bartenstein, Karlheinz Baumann, Mario M. Dorostkar, Axel Rominger, Paul Cumming, Michael Willem, Helmuth Adelsberger, Jochen Herms, Matthias Brendel
Journal: Theranostics (2021)

Modulation of the innate immune system is emerging as a promising therapeutic strategy against Alzheimer's disease (AD).However, determinants of a beneficial therapeutic effect are ill-understood.Thus, we investigated the potential of 18 kDa translocator protein positron-emission-tomography (TSPO-PET) for assessment of microglial activation in mouse brain before and during chronic immunomodulation.Methods: Serial TSPO-PET was performed during five months of chronic microglia modulation by stimulation of the peroxisome proliferator-activated receptor (PPAR)-γ with pioglitazone in two different mouse models of AD (PS2APP, App NL-G-F ).Using mixed statistical models on longitudinal TSPO-PET data, we tested for effects of therapy and sex on treatment response.We tested correlations of baseline with longitudinal measures of TSPO-PET, and correlations between PET results with spatial learning performance and β-amyloid accumulation of individual mice.Immunohistochemistry was used to determine the molecular source of the TSPO-PET signal.Results: Pioglitazone-treated female PS2APP and App NL-G-F mice showed attenuation of the longitudinal increases in TSPO-PET signal when compared to vehicle controls, whereas treated male App NL-G-F mice showed the opposite effect.Baseline TSPO-PET strongly predicted changes in microglial activation in treated mice (R = -0.874,p < 0.0001) but not in vehicle controls (R = -0.356,p = 0.081).Reduced TSPO-PET signal upon pharmacological treatment was associated with better spatial learning despite higher fibrillar β-amyloid accumulation.Immunohistochemistry confirmed activated microglia to be the source of the TSPO-PET signal (R = 0.952, p < 0.0001).Conclusion: TSPO-PET represents a sensitive biomarker for monitoring of immunomodulation and closely reflects activated microglia.Sex and pre-therapeutic assessment of baseline microglial activation predict individual immunomodulation effects and may serve for responder stratification.
Stepwise Evolution and Exceptional Conservation of ORF1a/b Overlap in Coronaviruses
Authors: Han Mei, Sergei Kosakovsky Pond, Anton Nekrutenko
Journal: Molecular Biology and Evolution (2021)

The programmed frameshift element (PFE) rerouting translation from ORF1a to ORF1b is essential for the propagation of coronaviruses. The combination of genomic features that make up PFE-the overlap between the two reading frames, a slippery sequence, as well as an ensemble of complex secondary structure elements-places severe constraints on this region as most possible nucleotide substitution may disrupt one or more of these elements. The vast amount of SARS-CoV-2 sequencing data generated within the past year provides an opportunity to assess the evolutionary dynamics of PFE in great detail. Here, we performed a comparative analysis of all available coronaviral genomic data available to date. We show that the overlap between ORF1a and ORF1b evolved as a set of discrete 7, 16, 22, 25, and 31 nucleotide stretches with a well-defined phylogenetic specificity. We further examined sequencing data from over 1,500,000 complete genomes and 55,000 raw read data sets to demonstrate exceptional conservation and detect signatures of selection within the PFE region.