tbuckley/cabot-search huggingface dataset:
Current and future strategies for the treatment of chronic hepatitis C
Authors: Omar Alshuwaykh, Paul Y. Kwo
Journal: Clinical and Molecular Hepatology (2020)

Chronic hepatitis C infection is a major cause of liver disease and hepatocellular carcinoma worldwide. While hepatitis C has been treated for decades with some success, the introduction of direct acting antiviral agents has revolutionized the treatment of hepatitis C with finite, highly effective, well-tolerated therapy and there are few populations that cannot be successfully treated now or are complicated to manage. The World Health Organization has released elimination targets in an effort to eliminate viral hepatitis and reduce dramatically the morbidity and mortality caused by both viral hepatitis. While hepatitis C is straightforward to treat, it remains problematic to eliminate on a global scale. Diagnosis of hepatitis C remains the major gap in the cascade of care and numerous screening strategies will be required to reduce this gap. While historically, treatment of hepatitis C has been centralized, decentralized approaches will be required to diagnose, evaluate, and link to care the large population of individuals worldwide with hepatitis C across low-, middle-, and high-income countries. With the introduction of multiple pangenotypic treatment options and reduced cost for these therapies, assessment and treatment for those with hepatitis C has been simplified and made more accessible worldwide. There are multiple populations for whom care models are being developed and refined, including those when inject drugs, those who are incarcerated, those who present with sexually transmitted disease including the men who have sex with men population, amongst many others. While a vaccine for hepatitis C remains elusive these efforts continue. Multiple successful elimination efforts have been reported.
Biomimetic nanoarchitecturing: A disguised attack on cancer cells
Authors: Adrija Jha, Ajinkya Nitin Nikam, Sanjay Kulkarni, Sadhana P Mutalik, Abhijeet Pandey, Manasa Hegde, Bola Sadashiva Satish Rao, Srinivas Mutalik
Journal: Journal of Controlled Release (2020)
Abstract 13414: Mechanisms of Endothelial Klf2-Mediated Pleiotropic Effects of Statins on the Prevention and Treatment of Tac-Induced Pathological Cardiac Remodeling
Authors: Hongda Li, Yanfang Wang, Yuzhen Zhang
Journal: Circulation (2019)

Rationale: Pathological cardiac fibrosis and hypertrophy, the common features of left ventricular remodeling, often progress towards heart failure. Statins, HMG-CoA reductase inhibitors, decrease c...
LTBK-01. INO-5401 AND INO-9012 DELIVERED INTRAMUSCULARLY (IM) WITH ELECTROPORATION (EP) IN COMBINATION WITH CEMIPLIMAB (REGN2810) IN NEWLY DIAGNOSED GLIOBLASTOMA
Authors: David A Reardon, Steven Brem, Arati Suvas Desai, Stephen Joseph Bagley, Sylvia Christine Kurz, Macarena Ines De La Fuente, Seema Nagpal, Mary Roberta Welch, Adilia Hormigo, Peter Forsyth, Jacob Mandell, Simon Khagi, Robert Aiken, Tobias Walbert, Frank Lieberman, Jana Portnow, James Batiste, Nicholas Carroll, Albert Sylvester, Patricia Campbell, Israel Lowy, Alex Dolgoter, Jean Boyer, Kimberly Kraynyak, Matthew P Morrow, Trevor McMullan, David B Weiner, Jeffrey Skolnik
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Novel T cell-enabling therapies, in combination with checkpoint inhibition, may improve OS in GBM. INO-5401 (synthetic DNA plasmids encoding hTERT, WT-1, PSMA) plus INO-9012 (synthetic DNA plasmid encoding IL-12), and the PD-1 immune checkpoint inhibitor cemiplimab, is given to patients with newly diagnosed GBM to evaluate tolerability, efficacy and immunogenicity. METHODS Phase I/II, single arm, 2 cohort study (A: MGMT unmethylated, B: MGMT methylated). Primary endpoint is safety; efficacy and immunogenicity are secondary. Nine mg INO-5401 plus 1 mg INO-9012 (every 3 weeks x 4 doses, then Q9W) is given IM with EP by CELLECTRA® 2000 with cemiplimab (350 mg IV Q3W). RT is given as 40 Gy over 3 weeks. TMZ is given with radiation (all patients), and adjuvantly (Cohort B only). RESULTS Fifty-two subjects enrolled: 32 in Cohort A; 20 in Cohort B. 35% women; median age 60 years (19–78 years). The adverse event profile is consistent with single-agent (INO-5401, INO-9012, EP and cemiplimab) reported events. OS at 12 months was 84.4% (Cohort A) and 85% (Cohort B). OS at 18 months in Cohort A is 50% (95% CI 31.9 - 68.1); median OS is 17.9 months (14.5 - NR); Cohort B OS18 and median OS will be presented. Tumor gene transcripts at diagnosis confirmed expression of INO-5401 antigens. Peripheral immune responses following INO-5401 revealed antigen-specific T cell responses by Interferon gamma ELISpot and flow cytometry, including cytokine production and expansion of antigen specific CD8+T cells with lytic potential. CONCLUSIONS INO-5401 + INO-9012, a novel DNA plasmid immunotherapy, demonstrates acceptable risk/benefit and generates robust systemic immune responses to encoded tumor antigens when administered with cemiplimab and RT/TMZ in newly diagnosed GBM patients. Overall survival is encouraging. Clinical trial information: NCT03491683.
RARE-08. CYST FLUID CYTOKINES MAY PROMOTE EPITHELIAL-TO-MESENCHYMAL TRANSITION IN PEDIATRIC ADAMANTINOMATOUS CRANIOPHARYNGIOMA
Authors: Trinka Vijmasi, Eric Prince, Astrid Hengartner, Chibueze Agwu, Susan Staulcup, Maryna Pavlova, Andrea Griesinger, Andrew Donson, Kathleen Dorris, Michael Handler, Todd Hankinson
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Despite poor clinical outcomes, no targeted therapies have been established for the treatment of Adamantinomatous Craniopharyngioma (ACP). The only known genetic aberration is a mutation in CTNNB1 that results in the nuclear accumulation of beta-catenin. Nuclear beta-catenin is an established inducer of Epithelial-to-Mesenchymal Transition (EMT). ACP cyst fluid is enriched with pro-inflammatory and SASP cytokines, many of which are also directly implicated in EMT. We sought to investigate the role of EMT in ACP pathology. METHODS Normal human epithelial cells were cultured and treated with ACP cyst fluid (10%) for 1, 2, 4 and 8 days. Cell morphology was monitored by live cell brightfield microscopy. The expression of EMT associated genes, ZEB1, ZEB2, SNAI-1, SLUG, TWIST, E-Cadherin, Beta-Catenin and Vimentin was determined by RT-qPCR. RESULTS ACP cyst fluid treated epithelial cells were markedly transformed into long, spindle-shaped cells. ACP cyst fluid treatment resulted in the progressive up-regulation of ZEB2 over 8 days (RQ=12.0; P&amp;lt;0.01), the progressive up-regulation of SNAI-1 over 4 days (RQ=5.1; P&amp;lt;0.05) and up-regulation of Vimentin (RQ=2.2; p&amp;lt;0.01), identified only on Day 8. CONCLUSION ACP cyst fluid can induce EMT-like changes in normal human epithelial cells. In conjunction with the frequency of beta-catenin mutation in ACP, it is possible that EMT plays a crucial role in the pathology of ACP. Understanding ACP pathology in the context of the EMT paradigm may aid the development of new targeted therapeutics.
Ectopic Pregnancy: 16-Year Survey of 905 Cases
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Stress Management during the Intracytoplasmic Sperm Injection Cycle May Slow Down First Embryo Cleavage and Accelerate Embryo Compaction: A Pilot Randomized Controlled Trial
Authors: Georges Raad, Judy Tanios, Simone Kerbaj, Youmna Mourad, Fadi Fakih, Fatmeh Shamas, Joseph Azouri, Chadi Fakih
Journal: Psychotherapy and Psychosomatics (2020)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; A firm consensus on the effectiveness of psychological interventions during infertility treatment has not been reached yet in terms of mental health and pregnancy rates. Moreover, the influence of these interventions on embryo cleavage kinetics has not been investigated. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; The aim of this work was to study whether stress management in couples undergoing an intracytoplasmic sperm injection (ICSI) cycle influences stress levels, mitochondrial DNA (mtDNA) levels in granulosa cells, and cleavage-stage embryos. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Infertile couples were randomized into a treatment as usual (TAU) group (&lt;i&gt;n&lt;/i&gt; = 30) and stress management program (SMP) group (&lt;i&gt;n&lt;/i&gt; = 29) at the beginning of an ICSI cycle. Couples in the SMP group attended education and relaxation sessions at each visit to the clinic for folliculometry. The perceived stress scale (PSS) was used to assess stress levels at the beginning and end of the cycle. Moreover, mtDNA levels of granulosa cells and embryo morphokinetics were evaluated. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Post-intervention, women in the SMP group had significantly lower PSS scores than their initial PSS (&lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.001; effect size, ES = 0.5) and than the final PSS of the TAU group (&lt;i&gt;p&lt;/i&gt; = 0.02; ES = 0.09). Additionally, mtDNA levels were significantly lower in luteal granulosa cells of the SMP group than the TAU group (&lt;i&gt;p&lt;/i&gt; = 0.02). An earlier time of pronuclei appearance (&lt;i&gt;p&lt;/i&gt; = 0.03) and time to 2 cells (&lt;i&gt;p&lt;/i&gt; = 0.015) and a faster time to full compaction (&lt;i&gt;p&lt;/i&gt; = 0.045) were detected in the embryos of the SMP group compared with the TAU group. &lt;b&gt;&lt;i&gt;Conclusion(s):&lt;/i&gt;&lt;/b&gt; The implemented program may reduce stress levels, retard first embryo cleavage, and accelerate embryo compaction. Further studies with an active control group are needed to confirm these results.
PHENOTYPIC DIVERGENCE OF JAGGED1 AND NOTCH2-ASSOCIATED ALAGILLE SYNDROME: RESULTS FROM THE INTERNATIONAL MULTICENTER GALA STUDY GROUP
Authors: Gala Study Grp, Shannon Vandriel, Liting Li, Huiyu She, Jian-She Wang, Melissa A. Gilbert, Nancy B. Spinner, Kathleen M. Loomes, David A. Piccoli, Lorenzo D'Antiga, Emanuele Nicastro, Pier Luigi Calvo, Winita Hardikar, Sahana Shankar, Rima L. Fawaz, Silvia Nastasio, Pinar Bulut, Irena Jankowska, Piotr Czubkowski, Dorota Gliwicz-Miedzinska, Etienne Sokal, Tanguy Demaret, Susan M. Siew, Michael Stormon, Florence Lacaille, Dominique Debray, Kyung Mo Kim, Woo Yim Baek, Jeffrey A. Feinstein, Noelle Ebel, Saul J. Karpen, Rene Romero, Palaniswamy Karthikeyan, Suzanne Davison, Henrik Arnell, Bjorn Fischler, James E. Squires, Henkjan J. Verkade, M. Kyle Jensen, Marianne Kavan, Amin J. Roberts, Helen M. Evans, Chatmanee Lertudomphonwanit, Way Seah Lee, Shikha S. Sundaram, Alexander Chaidez, Ryan T. Fischer, Yael Mozer-Glassberg, Catherine Larson-Nath, Henry Lin, Luis Bujanda
Journal: Hepatology (2020)
GCT-64. TREATMENT RESULTS IN CHILDREN WITH LOCALIZED CNS NGGCT
Authors: Irina Vilesova, Ekaterina Tarasova, Andge Valiakhmetova, Ekaterina Salnikova, Alexey Pshonkin, Galina Novichkova, Alexander Karachunsky, Ludmila Papusha
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND/OBJECTIVES Treatment of children with CNS NGGCT remains challenge: 5y OS is 60 – 80%; relapses are very aggressive. DESIGN/METHODS Between 2003 and 2019, 14 children (median age 10.5, range 4 – 16 years) with localized intracranial NGGCT were treated with RT after induction chemotherapy (focal – 4, WVI+boost – 6, WBI+boost – 3, CSI+boost – 1). Tumor markers were elevated in 13 patients: 6 – AFP, 5 – HCG, 2 – both. One patient with level of HCG 72049 IU/l in serum and 121451 IU/l in CSF received 4 cycles of PEI + CSI 30 Gy with boost 54Gy. RESULTS At a median follow-up of 4,7 years (range 1 – 16,25 years), 12 patients are alive. 5-year PFS and OS are 77,1% and 85,7%, respectively. Two patients (both AFP and HCG) progressed during RT (1 – focal, 1 – WBI+boost), both died. Two patients with high level of HCG recurred after therapy (WVI+boost – 1, focal – 1), both are alive. The first of them at recurrence (mts of lateral ventricle) received 4 cycles of PEI and RT (WBI+boost). The second patient had level of HCG 620IU/l and initially received focal irradiation 54Gy. At recurrence with distant spinal mts he received HD-CHT with auto-SCT, surgical resection of residual tumor and CSI with boost. CONCLUSIONS Good results of treatment of localized CNS NGGCT with CSI, WBI or WVI in compare with focal RT show advantages of extended irradiation field. CSI should be considered for patients with extremely high levels of tumor markers and respectively poor prognostic histology.
NIMG-32. THE PREDICTIVE CAPACITY OF PRE-OPERATIVE IMAGING ANALYSIS IN DIFFUSE GLIOMA: A COMPARISON OF CONNECTOMICS, RADIOMICS, AND CLINICAL PREDICTIVE MODELS
Authors: Rebecca Harrison, Bryce Wei Quan Tan, Hong Qi Tan, Lloyd Tan, Mei Chin Lim, Clement Yong, John Kuo, Shelli Kesler
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Radiomics and connectome analysis are distinct and non-invasive methods of deriving biologic information from MRI. Radiomics analyzes features intrinsic to the tumor, and connectomics incorporates data regarding the tumor and surrounding neural circuitry. In this study we used both techniques to predict glioma survival. METHODS We retrospectively identified 305 adult patients with histopathologically confirmed WHO grade II–IV gliomas who had presurgical, 3D, T1-weighted brain MRI. Available clinical variables included tumor lobe, hemisphere, multifocal nature grade, histology extent of surgical resection, patient age gender. For connectomics, we calculated nodal efficiencies, network size and degree for all pairs of 33 voxel cubes spanning the entire gray matter volume using similarity-based extraction and graph theory. Radiomic features were extracted using Pyradiomics and subjected to patient-level and population-level clustering (N=172). These clusters were then used to construct a multi-regional spatial interaction matrix for model building. Cox proportional hazards models were fit for clinical variables alone, connectomics alone, radiomics alone, connectomics+clinical and radiomics+clinical. We implemented 10-folds cross-validation and examined the mean area under the curve (AUC) across validation loops. RESULTS Median survival time was 134.2 months. The mean AUC for the clinical model was 0.79 +/- 0.01, the connectome model was 0.88 +/- 0.01, the combined connectome + clinical model was 0.93 +/- 0.01, the radiomic model was 0.64 +/- 0.05 and the radiomics+clinical model was 0.89+/-0.03. Radiomic analysis of the entire dataset as well as comparisons of radiomic+connectomics +/- clinical models are pending. CONCLUSIONS The combination of clinical variables and connectome analysis provided a more robust predictive model than other models. This suggests that connectome analysis incorporates valuable clinically-predictive information which can augment our capacity for prognostication of patients with diffuse glioma. These methods warrant further evaluation in larger prospective study of patients with diffuse glioma.
How Response Styles Moderate the Relationship between Daily Stress and Social Interactions in Depression, Social Phobia, and Controls
Authors: Andrew T. Gloster, Jürgen Hoyer, Maria Karekla, Andrea Meyer, Klaus Bader, Christian Imboden, Thorsten Mikoteit, Martin Hatzinger, Roselind Lieb
Journal: Psychotherapy and Psychosomatics (2020)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Stress and social isolation are potent predictors of negative health outcomes and are impacted in mood and anxiety disorders. Difficulties in social interactions have been particularly noted in people diagnosed with major depression disorder (MDD) and social phobia (SP). It remains poorly understood, however, how these variables interact on a moment-to-moment basis and which variables moderate this relationship. Psychological flexibility, or the ability to be open to experiences while maintaining engagement in valued activities, may help moderate the relationship between stress and social interaction. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; This study examined these variables in participants diagnosed with MDD and SP and compared them to a control group. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Participants were diagnosed with a mental disorder (&lt;i&gt;n&lt;/i&gt; = 118 MDD; &lt;i&gt;n&lt;/i&gt; = 47 SP) or were in the control group consisting of participants without MDD or SP (&lt;i&gt;n&lt;/i&gt; = 119). Using the event sampling methodology (ESM), participants were queried six times per day for 7 days about stress, social interactions, and emotional response (rigid vs. flexible). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Higher current stress levels were related to more social interactions. This relationship was even stronger in situations when response flexibility was increased, especially in the clinical groups. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Data suggest that a healthy psychological process (flexible emotional responding) buffers the relationship between stress and social interactions. We discuss how these variables interact and whether these patterns may paradoxically contribute to the maintenance of psychopathology.
Restoration of Hypoglycemia Awareness Alters Brain Activity in Type 1 Diabetes
Authors: Munachiso Nwokolo, Stephanie A. Amiel, Owen O’Daly, Ian A. Macdonald, Fernando O. Zelaya, Pratik Choudhary
Journal: Diabetes Care (2020)

OBJECTIVE Impaired awareness of hypoglycemia (IAH) in type 1 diabetes (T1D) is a major risk factor for severe hypoglycemia (SH) and is associated with atypical responses to hypoglycemia in brain regions involved in arousal, decision making, and memory. Whether restoration of hypoglycemia awareness alters these responses is unknown. We sought to investigate the impact of awareness restoration on brain responses to hypoglycemia. RESEARCH DESIGN AND METHODS Twelve adults with T1D and IAH underwent pseudocontinuous arterial spin labeling functional MRI during a hypoglycemic clamp (5–2.6 mmol/L) before and after a hypoglycemia avoidance program of structured education (Dose Adjustment for Normal Eating), specialist support, and sensor-augmented pump therapy (Medtronic MiniMed 640G). Hypoglycemic cerebral blood flow (CBF) responses were compared pre- and postintervention using predefined region-of-interest analysis of the thalamus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and hippocampus. RESULTS Postintervention, Gold and Clarke scores fell (6.0 ± 1.0 to 4.0 ± 1.6, P = 0.0002, and 5.7 ± 1.7 to 3.4 ± 1.8, P = 0.0008, respectively), SH rates reduced (1.5 ± 2 to 0.3 ± 0.5 episodes per year, P = 0.03), hypoglycemic symptom scores increased (18.8 ± 6.3 to 27.3 ± 12.7, P = 0.02), and epinephrine responses did not change (P = 0.2). Postintervention, hypoglycemia induced greater increases in ACC CBF (P = 0.01, peak voxel coordinates [6, 40, −2]), while thalamic and OFC activity did not change. CONCLUSIONS Increased blood flow is seen within brain pathways involved in internal self-awareness and decision making (ACC) after restoration of hypoglycemia awareness, suggesting partial recovery of brain responses lost in IAH. Resistance of frontothalamic networks, involved in arousal and emotion processing, may explain why not all individuals with IAH achieve awareness restoration with education and technology alone.
A Systematic Review and Meta-analysis of Local Salvage Therapies After Radiotherapy for Prostate Cancer (MASTER)
Authors: Luca F. Valle, Eric J. Lehrer, Daniela Markovic, David Elashoff, Rebecca Levin-Epstein, R. Jeffery Karnes, Robert E. Reiter, Matthew Rettig, Jeremie Calais, Nicholas G. Nickols, Robert T. Dess, Daniel E. Spratt, Michael L. Steinberg, Paul L. Nguyen, Brian J. Davis, Nicholas G. Zaorsky, Amar U. Kishan
Journal: European Urology (2020)
Battle for supremacy: nucleic acid interactions between viruses and cells
Authors: Elizabeth J. Hennessy, Garret A. FitzGerald
Journal: Journal of Clinical Investigation (2020)

Since the COVID-19 pandemic swept across the globe, researchers have been trying to understand its origin, life cycle, and pathogenesis. There is a striking variability in the phenotypic response to infection with SARS-CoV-2 that may reflect differences in host genetics and/or immune response. It is known that the human epigenome is influenced by ethnicity, age, lifestyle, and environmental factors, including previous viral infections. This Review examines the influence of viruses on the host epigenome. We describe general lessons and methodologies that can be used to understand how the virus evades the host immune response. We consider how variation in the epigenome may contribute to heterogeneity in the response to SARS-CoV-2 and may identify a precision medicine approach to treatment.
CTIM-04. UPDATES FOR A PHASE 2 OPEN-LABELED STUDY OF PEMBROLIZUMAB PLUS TTFIELDS PLUS MAINTENANCE TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA (2-THE-TOP)
Authors: Ashley Ghiaseddin, Sonisha Warren, Annie Allen, Deborah Sampson, Dongjiang Chen, Alexandra Sherman, Valerie Greene, Maryam Rahman, David Tran
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Tumor-treating fields (TTFields) are a new standard anti-mitotic treatment for newly diagnosed glioblastoma (ndGBM). Emerging data indicate that TTFields also stimulate innate immunity, leading to adaptive immunity. We hypothesize that immune checkpoint inhibitors synergize with TTFields to promote anti-tumor immunity in ndGBM. METHODS 24 adult patients with ndGBM will be enrolled following radiotherapy with concurrent temozolomide. To identify TTFields-induced immune effects that are augmented by pembrolizumab, TTFields (200 kHz) is started with cycle 1 of maintenance TMZ while pembrolizumab (200mg Q3W) is added at cycle 2 and continued up to 2 years or until disease progression or unacceptable toxicities. The primary endpoint is PFS vs. historical controls (JAMA, 318:2306–2316). Secondary endpoints include toxicity/tolerability and immune activation by TTFields before and after pembrolizumab as determined by single-cell analysis of peripheral blood mononuclear cells. RESULTS As of 06/19/2020, there are 17 evaluable patients. The median follow-up is 12.2 months from cycle 1 of maintenance TMZ. 10 (59%) patients are progression-free, and 13 (76%) are alive. Of 9 patients with follow-up &amp;gt; 12 months, the median PFS is at least 11.2 months vs. historical median PFS of TTFields plus maintenance TMZ of 6.7 months. The most common serious adverse events are pain, weakness, lymphatic swelling, and metabolic disturbances observed in 3 (18%), 2 (12%), 2 (12%), and 1 (6%) patients, respectively. In response to TTFields, we detect a 2.26 (p=0.01) and 5.2-fold (p=0.07) mean increase in the number of classical and plasmacytoid dendritic cells (DC), respectively. Network analysis shows wide-spread pathway upregulation in responders, especially type 1 interferon response genes in DC (FDR=0.02) and cytotoxicity genes in CD8 T cells (FDR=0.03). CONCLUSIONS Pembrolizumab in combination with TTFields plus maintenance TMZ is generally well tolerated in patients with ndGBM. Preliminary data demonstrates activation of adaptive immunity and improved efficacy and will be updated.