tbuckley/cabot-search huggingface dataset:
Identification of Adverse Risk Factors for Survival in Acquired Pure Red Cell Aplasia Receiving Immunosuppressive Therapy By the Japan PRCA2004/2006 Study and Introduction to the New Cohort Study PRCA2016
Authors: Makoto Hirokawa, Naohito Fujishima, Masanao Teramura, Kenichi Sawada, Masami Bessho, Kazuo Dan, Hisashi Tsurumi, Shinji Nakao, Akio Urabe, Shin Fujisawa, Yuji Yonemura, Fumio Kawano, Koichi Sugimoto, Akira Matsuda, Masamitsu Karasawa, Ayako Arai, Norio Komatsu, Hideo Harigae, Kaoru Tohyama, Saito-Moriya Akiko, Itaru Matsumura, Mitsuhiro Omine, Keiya Ozawa, Mineo Kurokawa, Shunya Arai, Kinuko Mitani
Journal: Blood (2017)
α-Helical cell-penetrating peptide-mediated nasal delivery of resveratrol for inhibition of epithelial-to-mesenchymal transition
Authors: Yumin Kim, Soyoung Hwang, Roza Khalmuratova, Sunah Kang, Mingyu Lee, Youngjun Song, Jong-Wan Park, Jaehoon Yu, Hyun-Woo Shin, Yan Lee
Journal: Journal of Controlled Release (2019)
Clinical Impact of Clonal and Subclonal TP53 Mutations and Deletions in Chronic Lymphocytic Leukemia: An Italian Multicenter Experience
Authors: Riccardo Bomben, Francesca Maria Rossi, Tiziana D'Agaro, Tamara Bittolo, Filippo Vit, Antonella Zucchetto, Erika Tissino, Federico Pozzo, Mario Ballerini, Pietro Bulian, Massimo Degan, Jerry Polesel, Eva Zaina, Ilaria Cattarossi, Paola Nanni, Hillarj Chivilò, Giovanni Francesco D'Arena, Enrico Santinelli, Annalisa Biagi, Annalisa Chiarenza, Francesco Zaja, Gabriele Pozzato, Francesco Di Raimondo, Davide Rossi, Giovanni Del Poeta, Valter Gattei
Journal: Blood (2019)
Overall survival with first-line durvalumab plus platinum-etoposide in patients with extensive-stage (ES)-SCLC in CASPIAN: Subgroup findings from Asia
Authors: M. Nishio, J.H. Ji, K. Hotta, C.-H. Chiu, J.-S. Lee, K. Azuma, S.-W. Kim, S.-Y. Wu, M. Dvorkin, D. Trukhin, L. Havel, M.J. Hochmair, M. Özgüroğlu, J. Bar, Y. Chen, J.W. Goldman, N. Byrne, P.J. Laud, N. Shire, L. Paz-Ares
Journal: Annals of Oncology (2019)
Management of Recurrent Acute Lymphoblastic Leukemia With T-Cell Engagement: CAR T, BiTEs, and Beyond
Authors: Jae Park
Journal: Journal of the National Comprehensive Cancer Network (2019)

Immunotherapies targeting CD19 (blinatumomab) and CD22 (inotuzumab ozogamicin) have demonstrated higher complete response rates and improved survival compared with chemotherapy in relapsed/refractory acute lymphoblastic leukemia (ALL), and are now standard of care in the relapsed setting. However, most adult patients still die of ALL despite these therapies, with or without hematopoietic stem cell transplant. At the NCCN 2019 Annual Congress: Hematologic Malignancies, Dr. Jae Park summarized clinical data from key trials of novel immunotherapies in ALL and reviewed evidence-based treatment approaches for adults with relapsed/refractory B‐cell ALL.
Selecting ß-Thalassemia Patients for Gene Therapy: A Decision-Making Algorithm
Authors: Donatella Baronciani, Maddalena Casale, Lucia De Franceschi, Giovanna Graziadei, Filomena Longo, Raffaella Origa, Valeria Maria Pinto, Paolo Rigano, Monia Marchetti, Antonia Gigante, Emanuele Angelucci, Maria Domenica Cappellini, Achille Iolascon, Antonio Piga, Gian Luca Forni
Journal: Blood (2019)
Spatio-temporal analysis of error-related brain activity in active and passive brain–computer interfaces
Authors: M. Mousavi, V. R. de Sa
Journal: Brain-Computer Interfaces (2019)

Electroencephalography (EEG)-based brain–computer interface (BCI) systems infer brain signals recorded via EEG without using common neuromuscular pathways. User brain response to BCI error is a contributor to non-stationarity of the EEG signal and poses challenges in developing reliable active BCI control. Many passive BCI implementations, on the other hand, have the detection of error-related brain activity as their primary goal. Therefore, reliable detection of this signal is crucial in both active and passive BCIs. In this work, we propose CREST: a novel covariance-based method that uses Riemannian and Euclidean geometry and combines spatial and temporal aspects of the feedback-related brain activity in response to BCI error. We evaluate our proposed method with two datasets: an active BCI for 1-D cursor control using motor imagery and a passive BCI for 2-D cursor control. We show significant improvement across participants in both datasets compared to existing methods.
The cell-adhesion and signaling molecule PECAM-1 as a molecular mediator of genotoxic chemotherapy resistance
Authors: Carmen Bergom, Cunji Gao, Shigemi Matsuyama, Peter J. Newman
Journal: Cancer Research (2005)

831  Many chemotherapeutic agents cause cytotoxicity by initiating apoptosis. Defects in apoptosis contribute to cancer therapy failure and the emergence of resistant disease. Identifying new molecules that confer resistance to cancer therapy allows design of strategies that restore drug sensitivity to resistant cancers. Platelet endothelial cell adhesion molecule-1 (PECAM-1), a homophilic binding member of the immunoreceptor tyrosine-based inhibitory motif (ITIM) family of inhibitory receptors, has previously been shown to potently suppress mitochondrial-dependent, Bax-mediated apoptosis. PECAM-1 expression has been reported on a variety of human malignancies, including leukemias, cervical cancer, multiple myeloma, angiosarcoma, salivary gland malignancy, and breast cancer, but the significance of this expression has not been well-defined. Here we show that PECAM-1 expression can inhibit apoptosis induced by the genotoxic chemotherapeutic agents cisplatin and etoposide. HEK293 and REN mesothelioma cells lacking PECAM-1 displayed much higher caspase activity and nuclear condensation after drug treatment than did cells expressing PECAM-1. The protective effect of PECAM-1 is, in part, mediated by the ITIM domains within its cytoplasmic tail, as mutation of ITIM tyrosines prevented full protection. In addition, a PECAM-1 mutant lacking homophilic binding ability was not fully protective. Thus, PECAM-1 appears to confer resistance to cell death via both cell-cell communication and intracellular signaling via its ITIM domains. Finally, when stable cell lines expressing PECAM-1 were treated with etoposide for 48 hours and subsequently cultured up to five weeks, the surviving cells had a greater than 40% increase in the median number of PECAM-1 molecules expressed on their surface when compared to untreated cells, indicating that cells with higher PECAM-1 expression are more likely to survive treatment with DNA-damaging chemotherapy. Taken together, these studies suggest PECAM-1 attenuates apoptosis in response to DNA damage and that this receptor is capable of conferring resistance to genotoxic chemotherapeutic agents. Furthermore, PECAM-1 expression on human malignancies may increase the likelihood of developing resistance to chemotherapeutic treatment, making this molecule a possible prognostic indicator of treatment response. Identifying ways in which to abolish PECAM-1’s protective effect may be an effective adjuvant therapy for patients whose cancers express this cell-surface molecule.
PDCT-18 (LTBK-03). PHASE I CLINICAL TRIAL WITH ONCOLYTIC VIRUS DNX-2401 FOR DIPGS
Authors: Ignacio Iñigo-Marco, Ricardo Díez-Valle, Marc Garcia-Moure, Ana Patiño-García, Marisol González Huarriz, Chris Jones, Candelaria Gomez-Manzano, Juan Fueyo, Marta M Alonso, Sonia Tejada
Journal: Neuro-Oncology (2019)

Abstract Delta-24-RGD (DNX-2401 in the clinic) has been tested for adult glioblastoma presenting a safe profile and promising efficacy. Our group has showed that the virus is safe and effective in preclinical models of pHGG and DIPG. Moreover, we showed that the virus is able to trigger an antitumor immune response. These results allowed us to propel a phase I clinical trial for newly diagnosed DIPGs (NCT03178032) where the patients received an intratumoral injection of DNX-2401 (N=12). Tumor biopsy is performed through the cerebellar peduncle, followed by virus injection using a cannula that prevents the reflux. The trial is uncontrolled, unicentric with a 3 + 3 design. The objective of this trial is to determine the safety, tolerability, and toxicity of DNX-2401 in subjects with DIPG. Secondary endpoints are overall survival at 12 months (OS12), percentage of responses and induced immune response against tumor. To date 9 patients have been treated within the trial. Three patients were treated with the D1=1x1010vp and because the lack of toxicity we escalated to the D2= 5x1010vp. The procedure was well tolerated and safe. Patients were home 3–4 days after the injection. All the patients displayed a reduced tumor volume after combined treatment. We performed molecular studies in 8 out of the 9 patients (RNAseq and a thermofisher pediatric panel). Subsequently we evaluated the immune cell composition in the tumor using multiplexed quantitative immunofluorescence on the biopsies pre-virus injection. T cells were hardly noticeable in these tumors while macrophages were abundant. Using a multiplexed TCR-sequencing mRNA-based assay to analyze 18 available paired pre- and post-treatment samples from the trial, we detected increased clonal T cell diversity following treatment with virus. In addition, we are assessing the existence of pre and post treatment neutralizing antibodies and its relationship with survival. Finally, we have performed functional studies using 2 cell lines isolated from patients included in this trials and confronting them with T-cells isolated from peripheral blood of the same patients before and after the treatment with the virus. Information acquired within this clinical study would aid to understand the response of DIPGs to viral therapies and therefore to better tailor this strategy to improve the survival of pediatric brain tumors.
Outcomes of Transcatheter Aortic Valve Replacement in Patients With Severe Aortic Stenosis
Authors: Marko T. Boskovski, Tom C. Nguyen, James M. McCabe, Tsuyoshi Kaneko
Journal: JAMA Surgery (2019)

Medically treated symptomatic severe aortic stenosis has poor outcomes, and in the past 6 decades, it has successfully been treated with surgical aortic valve replacement (SAVR). However, one-third of patients with indications for SAVR are not offered surgery because of the high risk of complications. Transcatheter aortic valve replacement (TAVR), initially developed as a less invasive treatment for inoperable patients, has successfully been used in healthier patient cohorts. In 2017, TAVR became the most common approach for aortic valve replacement in the United States.During the past decade, the Placement of Aortic Transcatheter Valve (PARTNER) trials (for balloon-expandable valves) and the CoreValve trials (for self-expandable valves) investigated the performance of TAVR in progressively lower-risk patient cohorts. The initial trials demonstrated TAVR to be superior (PARTNER B) and noninferior (CoreValve Extreme Risk) to optimal medical therapy in inoperable patients. Subsequent trials showed both balloon-expandable and self-expandable valves to have good results in high-risk, medium-risk, and low-risk surgical patients when compared with SAVR. However, owing to the fundamentally different nature of the procedure, some complications have been more prevalent with TAVR, most notably moderate or severe paravalvular leak, conduction abnormalities necessitating permanent pacemaker placement, and vascular complications. When present, these complications have been associated with worse outcomes.The results of the groundbreaking TAVR trials from the past decade have led to a revolution in the treatment of aortic stenosis. There are now 3 US Food and Drug Administration-approved TAVR devices, and with the encouraging results from the latest low-risk trials, TAVR is likely going to become the dominant treatment for symptomatic severe aortic stenosis. New devices on the horizon are looking to improve the complication rates of TAVR, and ongoing trials are looking to further expand the indications of TAVR and answer 1 of the main remaining questions, ie, long-term durability of percutaneously placed devices.
Activating mutations in CSF1R and additional receptor tyrosine kinases in histiocytic neoplasms
Authors: Benjamin H. Durham, Estibaliz Lopez Rodrigo, Jennifer Picarsic, David Abramson, Veronica Rotemberg, Steven De Munck, Erwin Pannecoucke, Sydney X. Lu, Alessandro Pastore, Akihide Yoshimi, Diana Mandelker, Ozge Ceyhan-Birsoy, Gary A. Ulaner, Michael Walsh, Mariko Yabe, Kseniya Petrova-Drus, Maria E. Arcila, Marc Ladanyi, David B. Solit, Michael F. Berger, David M. Hyman, Mario E. Lacouture, Caroline Erickson, Ruth Saganty, Michelle Ki, Ira J. Dunkel, Vicente Santa-María López, Jaume Mora, Julien Haroche, Jean-Francois Emile, Olivier Decaux, Frederic Geissmann, Savvas N. Savvides, Alexander Drilon, Eli L. Diamond, Omar Abdel-Wahab
Journal: Nature Medicine (2019)
Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation
Authors: Alan T. Tang, Katie R. Sullivan, Courtney C. Hong, Lauren M. Goddard, Aparna Mahadevan, Aileen Ren, Heidy Pardo, Amy Peiper, Erin Griffin, Ceylan Tanes, Lisa M. Mattei, Jisheng Yang, Li Li, Patricia Mericko-Ishizuka, Le Shen, Nicholas Hobson, Romuald Girard, Rhonda Lightle, Thomas Moore, Robert Shenkar, Sean P. Polster, Claudia J. Rödel, Ning Li, Qin Zhu, Kevin J. Whitehead, Xiangjian Zheng, Amy Akers, Leslie Morrison, Helen Kim, Kyle Bittinger, Christopher J. Lengner, Markus Schwaninger, Anna Velcich, Leonard Augenlicht, Salim Abdelilah-Seyfried, Wang Min, Douglas A. Marchuk, Issam A. Awad, Mark L. Kahn
Journal: Science Translational Medicine (2019)

Cerebral cavernous malformation (CCM) is a genetic, cerebrovascular disease. Familial CCM is caused by genetic mutations in KRIT1, CCM2, or PDCD10 Disease onset is earlier and more severe in individuals with PDCD10 mutations. Recent studies have shown that lesions arise from excess mitogen-activated protein kinase kinase kinase 3 (MEKK3) signaling downstream of Toll-like receptor 4 (TLR4) stimulation by lipopolysaccharide derived from the gut microbiome. These findings suggest a gut-brain CCM disease axis but fail to define it or explain the poor prognosis of patients with PDCD10 mutations. Here, we demonstrate that the gut barrier is a primary determinant of CCM disease course, independent of microbiome configuration, that explains the increased severity of CCM disease associated with PDCD10 deficiency. Chemical disruption of the gut barrier with dextran sulfate sodium augments CCM formation in a mouse model, as does genetic loss of Pdcd10, but not Krit1, in gut epithelial cells. Loss of gut epithelial Pdcd10 results in disruption of the colonic mucosal barrier. Accordingly, loss of Mucin-2 or exposure to dietary emulsifiers that reduce the mucus barrier increases CCM burden analogous to loss of Pdcd10 in the gut epithelium. Last, we show that treatment with dexamethasone potently inhibits CCM formation in mice because of the combined effect of action at both brain endothelial cells and gut epithelial cells. These studies define a gut-brain disease axis in an experimental model of CCM in which a single gene is required for two critical components: gut epithelial function and brain endothelial signaling.
Treatment Effect of Omalizumab on Severe Pediatric Atopic Dermatitis
Authors: Susan Chan, Victoria Cornelius, Suzie Cro, John I. Harper, Gideon Lack
Journal: JAMA Pediatrics (2019)

Systemic treatments for severe childhood atopic dermatitis have limited evidence and/or are unlicensed. Despite the efficacy of anti-IgE medication (omalizumab) in the treatment of atopy, no large randomized studies in childhood atopic dermatitis have been published.To determine the effectiveness of omalizumab in treating severe atopic dermatitis in children.The Atopic Dermatitis Anti-IgE Pediatric Trial (ADAPT) was a 24-week single-center, double-blind, placebo-controlled randomized clinical trial with a 24-week follow-up. Conducted from November 20, 2014, to August 31, 2017, at Guy's and St Thomas' Hospital NHS Foundation Trust and King's College London in the United Kingdom, this trial recruited participants after a screening visit. Eligible participants (n = 62) were aged 4 to 19 years and had severe eczema (with objective Scoring Atopic Dermatitis [SCORAD] index >40) that was unresponsive to optimum therapy. Statistical analysis was conducted using the intention-to-treat principle.Subcutaneous omalizumab or placebo for 24 weeks. The drug manufacturer's dosing tables were used to determine the dosage based on total IgE (30-1500 IU/mL) and body weight (in kilograms) at randomization.Objective SCORAD index after 24 weeks of treatment.In total, 62 children (mean [SD] age, 10.3 [4.2] years; 32 (52%) were male) were randomized to either omalizumab (n = 30) or placebo (n = 32). Five participants withdrew from treatment (4 [13%] from the placebo group, and 1 [3%] from the omalizumab group). Follow-up attendance was 97% at week 24 and 98% at week 48. After adjustment for baseline objective SCORAD index, age, and IgE level, the mean difference in objective SCORAD index improvement between groups at week 24 was -6.9 (95% CI, -12.2 to -1.5; P = .01), significantly favoring omalizumab therapy and reflecting the results in other assessments of atopic dermatitis severity. Improved quality-of-life scores were seen in the omalizumab group, as measured by the Children's Dermatology Life Quality Index/Dermatology Life Quality Index (-3.5; 95% CI, -6.4 to -0.5) and Pediatric Allergic Disease Quality of Life Questionnaire score (-0.5; 95% CI, -0.9 to -0.0). Improvements in disease severity occurred despite lower potent topical corticosteroid use in the omalizumab group compared with the placebo group (median [interquartile range (IQR)] percentage of body surface area covered, 16% [10%-46%] vs 31% [14%-55%]; median [IQR] number of days of use, 109 [34-164] days vs 161 [82-171] days).This randomized clinical trial found that omalizumab significantly reduced atopic dermatitis severity and improved quality of life in a pediatric population with atopy and severe eczema despite highly elevated total IgE levels at baseline. The result was associated with a potent topical corticosteroid sparing effect and may suggest that omalizumab is a treatment option for difficult-to-manage severe eczema in children with atopy.ClinicalTrials.gov identifier: NCT02300701.
The Inner Lives of Doctors: Physician Emotion in the Care of the Seriously Ill
Authors: Julie Childers, Bob Arnold
Journal: The American Journal of Bioethics (2019)

Elisabeth Kübler-Ross' seminal 1969 work, On Death and Dying, opened the door to understanding individuals' emotional experiences with serious illness and dying. Patient's emotions, however, are only half the story in the patient-physician relationship. In recent years physicians' emotional reactions have gotten more attention. These sometimes-unacknowledged emotions influence how we approach our work, including life and death decisions. This article reviews some of the main emotions physicians experience when caring for seriously ill and dying patients and the challenges physicians face in regulating their emotions in a professional setting. We also discuss some of the ways that physician emotion may influence medical decision-making and contribute to conflict. Attention to the emotional level of physician experience may promote better care.
Uncertainty and interpretability in convolutional neural networks for semantic segmentation of colorectal polyps
Authors: Kristoffer Wickstrøm, Michael Kampffmeyer, Robert Jenssen
Journal: Medical Image Analysis (2019)

Convolutional Neural Networks (CNNs) are propelling advances in a range of different computer vision tasks such as object detection and object segmentation. Their success has motivated research in applications of such models for medical image analysis. If CNN-based models are to be helpful in a medical context, they need to be precise, interpretable, and uncertainty in predictions must be well understood. In this paper, we develop and evaluate recent advances in uncertainty estimation and model interpretability in the context of semantic segmentation of polyps from colonoscopy images. We evaluate and enhance several architectures of Fully Convolutional Networks (FCNs) for semantic segmentation of colorectal polyps and provide a comparison between these models. Our highest performing model achieves a 76.06\% mean IOU accuracy on the EndoScene dataset, a considerable improvement over the previous state-of-the-art.
Pain management in patients undergoing treatment for head and neck cancer with opiate use disorder on medication-assisted treatment.
Authors: Dana Guyer, Ariel E. Birnbaum, Kara Lynne Leonard, Esther Yu
Journal: Journal of Clinical Oncology (2019)

120 Background: Buprenorphine, a partial agonist at the mu opiate receptor, is an effective pain medication and use has increased for patients with cancer pain, especially those with concurrent opiate use disorder (OUD). Substance use disorder is common in head and neck cancer patients since alcohol and tobacco are predisposing factors. Definitive chemoradiation (chemoRT) for head and neck cancer is a difficult treatment with a high burden of symptoms, including mucositis pain, dysphagia and odynophagia. Patients undergoing concurrent chemoRT routinely require systemic opiates to manage pain and tolerate treatment. This is a review of our institution’s experience using buprenorphine and methadone for pain management in patients with OUD during chemoRT for head and neck cancer. Methods: We reviewed all cases seen in the Lifespan Cancer Institute head and neck cancer multidisciplinary clinic between July 2018 and June 2019. Approximately 40% of patients had a history of opiate use disorder and one-fifth of those were on medication-assisted treatment with buprenorphine or methadone. The charts of patients with OUD were reviewed with respect to history of buprenorphine or methadone use, pain scores during chemoRT, effectiveness of pain medications during chemoRT, and change of pain medication during treatment. Results: 5 patients on buprenorphine and 4 patients on methadone underwent treatment with chemoRT for head and neck cancer. Despite effectiveness for pain with other cancer patients, we did not find that buprenorphine was an effective opiate for patients undergoing chemoRT for head and neck cancer. All patients on buprenorphine had to be rotated off to another opiate (generally methadone) to achieve adequate pain relief. Median time to pain medication change was 3 weeks (range: prior to starting to week 5/7). The patients on methadone generally were able to tolerate treatment with minor adjustments to their methadone. Conclusions: The ceiling effect of buprenorphine that makes it effective for OUD is a barrier to managing the severe pain from chemoRT for head and neck cancer, while methadone is effective for both pain control and maintenance of sobriety during a taxing treatment.
The Impact and Modulation of Microenvironment-Induced Immune Resistance Against CAR T Cell and Antibody Treatments in Multiple Myeloma
Authors: Lisa C. Holthof, Hilma J. Van Der Horst, Renée Poels, Jort T. van der Schans, Anne T. Gelderloos, Fengzhi Li, Henk Lokhorst, Sonja Zweegman, Maria Themeli, Niels W. C. J. Van De Donk, Richard W.J. Groen, Tuna Mutis
Journal: Blood (2019)