tbuckley/cabot-search huggingface dataset:
Association of Vitamin D Deficiency with Inferior Treatment Outcomes in Patients with Newly Diagnosed Classic Hodgkin Lymphoma: MD Anderson Cancer Center Experience
Authors: Ranjit Nair, Samer Al Hadidi, Raphael Eric Steiner, Sairah Ahmed, Paolo Strati, Simrit Parmar, Swaminathan P Iyer, Penny Fang, Jillian R. Gunther, Preetesh Jain, Chelsea C. Pinnix, Bouthaina S. Dabaja, Yago Nieto, Felipe Samaniego, Branko Cuglievan, Roberto N. Miranda, L. Jeffrey Medeiros, Lei Feng, Hubert Chuang, Michael Wang, Hun Ju Lee
Journal: Blood (2020)
Easix As Prediction Score before CAR-T Cells Vs Allogeneic Hematopoietic Cell Transplantation (alloHCT) for Relapsed/Refractory (r/r) Large B Cell Lymphoma (LBCL)
Authors: Felix Korell, Thomas Luft, Michael Schmitt, Sascha Dietrich, Anita Schmitt, Carsten Mueller-Tidow, Peter Dreger
Journal: Blood (2020)
Financial Toxicity Intervention Decreases Mortality in High Risk Hematologic Malignancy Patients
Authors: Thomas G. Knight, Melissa Aguiar, Myra Robinson, Allison Martin, Tommy Chen, Rupali Bose, Jing Ai, Brittany K. Ragon, Aleksander L. Chojecki, Nilay A. Shah, Srinivasa R. Sanikommu, James Symanowski, Edward A Copelan, Michael R. Grunwald
Journal: Blood (2020)
Efficacy of High Dose Chemotherapy with Autologous Transplantation for Primary CNS Lymphoma Treatment
Authors: Muhammad Khawar Sana, Syed Maaz Abdullah, Muhammad Tayyeb, Mohammad Ammad Ud Din, Amrat Ehsan, Abdul Jabbar Dar, Qasim Khurshid, Sikander Abdullah, Karun Neupane, Mobeen Zaka Haider, Muhammad Jahanzeb Khalil, Hamid Ehsan, Syed Ziauddin A Zaidi, Faiz Anwer
Journal: Blood (2020)
SAT0258 Disease related characteristics do not influence willingness to participate in a large clinical trial in rheumatoid arthritis (ra)
Authors: Z De Jong, M Munneke, A Jansen, TP Vliet Vlieland, JM Hazes
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> A major problem in the incorporation of results from clinical trials in daily practice is that demographic and clinical characteristics of patients who participate in clinical trials differ significantly from those of non-participants. It is not known if this limited generalizability of trial results is also present in trials with RA patients. <h3>Objectives</h3> To investigate whether demographic or clinical characteristics of RA patients are a barrier to participation in a trial. In order to detect such an effect we investigated the recruitment of RA patients for a trial on the effectiveness of a long-term high intensity weight-bearing exercise programme. <h3>Methods</h3> Medical records of all known RA patients from four cooperating centres were screened for eligibility (ARA 1987 revised criteria, 20–70 years, ACR functional class I-III, stable DMARD in the past 3 months, no prosthesis of a weight bearing joint, no serious comorbidity). Eligible patients received extensive written information and were invited for an information meeting. The investigators subsequently screened all patients who wished to participate to ensure the eligibility and a personalised approach. Participants as well as non-participants were mailed a questionnaire containing questions on socio-demographic and disease-related characteristics, comorbidity and experience with participation in clinical trials in the past. Questionnaires concerning functional status (HAQ), utility (EuroQol) and quality of life (RAQol) were added. Differences between participants and non-participants were tested with Mann-Whitney test or Chi-square test where appropriate. <h3>Results</h3> 299 of the 300 participants (99.7%) and 892 of the 1191 non-participants (74.9%) returned the questionnaires completed. Participants were younger (median 54 vs. 57 yrs, p &lt; 0.005), more often female (79 vs. 73%, p &lt; 0.05) and the disease duration was slightly shorter (median 6 vs. 8 yrs, p &lt; . 005). Participants and non-participants did not differ with respect to the presence of rheumatoid factor and erosions, previous and current use of medication, perception of burden of illness, comorbidity, experience with participation in clinical trials in the past, functional status, utility, and quality of life measures. <h3>Conclusion</h3> Disease related characteristics do not influence the willingness to participate in a clinical trial on the effect of long-term high intensity exercise therapy. The slight differences in sociodemographic characteristics between participants and non-participants do not seem clinically relevant. The recruitment strategy in which all eligible patients were approached in a non-selective, unbiased way may have contributed to this favourable result.
FRI0027 5-aminolevulinic acid induced protoporphyrin ix formation in arthritic synovial tissues: an approach for synovial photodynamic therapy in arthritis
Authors: G Kirdaite, N Lange, N Busso, H Van den Bergh, P Kucera, A So
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To determine the optimal conditions for synovial accumulation of protoporphyrin IX (PpIX) and light induced synovial cytotoxicity in arthritis <i>in vitro</i> and <i>in vivo</i>. <h3>Methods</h3> In vitro studies: Synovial biopsies from patients with osteoarthritis (OA, n = 9), rheumatoid arthritis (RA, n = 3) and synovial tissues from mice with antigen-induced arthritis (AIA, n = 9) were incubated with different concentrations of 5-aminolevulinic acid hexyl-ester (h-ALA), a protoporphyrin IX (PpIX) precursor. Tissue PpIX content was determined by microspectrofluorometry. Following photoexcitation, the synovial tissues were evaluated by Sytox-Green fluorescence for cell death. Animal studies: h-ALA was injected intra-articularly into knee joints of mice with AIA (n = 40). Following photodynamic therapy (PDT) <i>in vivo</i>, joint inflammation was assessed by technetium scintigraphy and histology. <h3>Results</h3> In human biopsies, the highest fluorescence intensity was observed after incubation with 0.5–1 mM h-ALA. Kinetic studies showed that PpIX accumulation in human tissues reached a peak at 3 h in OA and increased linearly up to 6 h in RA. Murine tissues showed highest fluorescence intensity at a concentration of 4 mM <i>in vitro</i> and 8 mM <i>in vivo</i>. By fluorescence microscopy, PpIX was localised to the synovial lining layer, endothelial cells and macrophages. Irradiation of pre-incubated tissues <i>in vitro</i> led to significant cell death. PDT <i>in vivo</i> in AIA led to a statistically significant reduction of histological parameters of joint damage in irradiated joints. <h3>Conclusion</h3> Our findings suggest that PDT based on PpIX accumulation in the synovial membrane may be a rational basis for photodynamic synovectomy in arthritic diseases.
Improvement in Non-Relapse Mortality Following Allogeneic Transplantation for Chronic Lymphocytic Leukaemia in Australia and New Zealand: An Australasian Bone Marrow Transplant Recipient Registry Study
Authors: Luani Barge, Steven Tran, Glen A Kennedy, David Ritchie, David Gottlieb, Sam Milliken, Andrew Spencer, Duncan Purtill, Travis Perera, Richard Doocey, Stephen R Larsen, Andrew Butler, Peter G Bardy, Matthew Greenwood, Simon Durrant, Cameron Curley, Caroline Stewart, Constantine S. Tam, Jenny Collins, Ian Bilmon, Pietro R Di Ciaccio, Sushrut S. Patil, Min-Hi Han, Nada Hamad
Journal: Blood (2020)
Neuronal Autophagy Regulates Presynaptic Neurotransmission by Controlling the Axonal Endoplasmic Reticulum
Authors: Marijn Kuijpers, Gaga Kochlamazashvili, Alexander Stumpf, Dmytro Puchkov, Aarti Swaminathan, Max Thomas Lucht, Eberhard Krause, Tanja Maritzen, Dietmar Schmitz, Volker Haucke
Journal: Neuron (2020)

Neurons are known to rely on autophagy for removal of defective proteins or organelles to maintain synaptic neurotransmission and counteract neurodegeneration. In spite of its importance for neuronal health, the physiological substrates of neuronal autophagy in the absence of proteotoxic challenge have remained largely elusive. We use knockout mice conditionally lacking the essential autophagy protein ATG5 and quantitative proteomics to demonstrate that loss of neuronal autophagy causes selective accumulation of tubular endoplasmic reticulum (ER) in axons, resulting in increased excitatory neurotransmission and compromised postnatal viability in vivo. The gain in excitatory neurotransmission is shown to be a consequence of elevated calcium release from ER stores via ryanodine receptors accumulated in axons and at presynaptic sites. We propose a model where neuronal autophagy controls axonal ER calcium stores to regulate neurotransmission in healthy neurons and in the brain.
High-Risk Multiple Myeloma Patients Are Missed without Gene Expression Profiling
Authors: Martin H Van Vliet, Yan-Ting Chen, Erik H Van Beers, Rowan Kuiper, Erik T. Valent, Marieke Spaan, Carolina Terragna, Elena Zamagni, Michele Cavo, Stefania Oliva, Alessandra Larocca, Torsten Haferlach, Wee-Joo Chng, Anders Waage, M Duin, Pieter Sonneveld
Journal: Blood (2020)
Derivation and Validation of a Novel Lipid Metabolism Level-Based Prognostic Scoring System, Enbc Score, for Newly Diagnosed Mature T and NK Cell Lymphoma
Authors: Tiange Lu, Xiaosheng Fang, Yujie Jiang, Jiarui Liu, Yiqing Cai, Shunfeng Hu, Mengfei Ding, Linquan Zhan, Xin Wang, Xiangxiang Zhou
Journal: Blood (2020)
Incidence rates of hospitalization and death from COVID-19 in patients with psoriasis receiving biological treatment: A Northern Italy experience
Authors: Paolo Gisondi, Stefano Piaserico, Luigi Naldi, Paolo Dapavo, Andrea Conti, Piergiorgio Malagoli, Angelo Valerio Marzano, Federico Bardazzi, Massimo Gasperini, Simone Cazzaniga, Antonio Costanzo, Lidia Sacchelli, Elena Pezzolo, Francesco Messina, Claudia Lasagni, Laura Bigi, Angelo Cattaneo, Carlo Giovanni Carrera, Luisa Arancio, Simone Ribero, Giulia Rozzo, Giovanni Damiani, Paola Facheris
Journal: Journal of Allergy and Clinical Immunology (2020)
Phase 1 Study of Escalating Doses of Ibrutinib and Temozolomide, Etoposide, Liposomal Doxorubicin, Dexamethasone, Rituximab (TEDDI-R) with Isavuconazole for Relapsed and Refractory Primary CNS Lymphoma
Authors: Mark Roschewski, Christopher Melani, Rahul Lakhotia, Stefania Pittaluga, James D. Phelan, Cody Peer, Michail S. Lionakis, Lydia L. Chou, Matthias Holdhoff, Michael Glantz, Jan Drappatz, Catherine Lai, John A. Butman, Andrea Nicole Lucas, Seth M. Steinberg, William D. Figg, Elaine S. Jaffe, S. Percy Ivy, Richard F. Little, Louis M. Staudt, Wyndham H. Wilson
Journal: Blood (2020)
Abstract 15748: Relationships Between Metaboreceptor Protein Expression and Metaboreflex Sensitivity in Healthy Adults
Authors: Joshua R Smith, Corey Hart, Joshua G Akinsanya, Ian R Lanza, Thomas P Olson
Journal: Circulation (2019)

Introduction: The exercise pressor reflex (EPR) contributes to cardiopulmonary adjustments during exercise including increased mean arterial pressure (MAP) and ventilation (VE). One arm of the EPR ...
Factors Affecting Lymphocyte Collection Efficiency and Manufactured Product Specification during Leukapheresis for Diffuse Large B Cell Lymphoma Patients Treated with Commercial Tisagenlecleucel
Authors: Ariel Perez Perez, Christina A Bachmeier, Renee Smilee, Albert J Ribickas, Aleksandr Lazaryan, Julio C. Chavez, Claudio Anasetti, Bijal Shah, Farhad Khimani, Taiga Nishihori, Marco L. Davila, Frederick L. Locke, Michael D. Jain, Hien D. Liu
Journal: Blood (2020)
Genome and Transcriptome Profiling of Monosomy 7 AML Defines Novel Risk and Therapeutic Cohorts
Authors: Rhonda E. Ries, Timothy Junius Triche, Jenny L. Smith, Amanda R. Leonti, Todd A. Alonzo, Jason E. Farrar, Xiaolong Chen, Yanling Liu, Timothy Shaw, Benjamin J. Huang, Yi-Cheng Wang, Robert B. Gerbing, Betsy A Hirsch, Susana C. Raimondi, Alan S. Gamis, Richard Aplenc, Jinghui Zhang, E. Anders Kolb, Xiaotu Ma, Soheil Meshinchi
Journal: Blood (2020)
Vessel Wall–Imaging Biomarkers of Carotid Plaque Vulnerability in Stroke Prevention Trials
Authors: Luca Saba, Alan R. Moody, Tobias Saam, M. Eline Kooi, Bruce A. Wasserman, Daniel Staub, Aad van der Lugt, J. Kevin DeMarco, David Saloner, Max Wintermark, Ajay Gupta
Journal: JACC. Cardiovascular imaging (2020)
<i>DNMT3A</i> clonal Hematopoiesis in Older Donors Is Associated with Improved Survival in Recipients after Allogeneic Hematopoietic Cell Transplant
Authors: Christopher J. Gibson, Haesook T. Kim, H. Moses Murdock, Bryan Hambley, Lin Zhao, Lisa Green, Mark Fleharty, Brendan Blumenstiel, Carrie Cibulskis, Christopher D Gocke, Sarah Nikiforow, Amy E. DeZern, Vincent T. Ho, Richard J. Jones, Niall Lennon, Jerome Ritz, Robert J. Soiffer, Lukasz P. Gondek, R. Coleman Lindsley
Journal: Blood (2020)
Lack of Association of Spontaneous Coronary Artery Dissection With Autoimmune Disease
Authors: Vanessa L. Kronzer, Alex D. Tarabochia, Angie S. Lobo Romero, Nicholas Y. Tan, Thomas J. O’Byrne, Cynthia S. Crowson, Tamiel N. Turley, Elena Myasoedova, John M. Davis, Claire E. Raphael, Rajiv Gulati, Sharonne N. Hayes, Marysia S. Tweet
Journal: Journal of the American College of Cardiology (2020)
Mesenchymal Stromal Cells (MSCs) Experience in France to Prevent Graft Failure after Hematopoietic Stem Cell Transplantation: A Retrospective Study from the MSCs/CTL Group of the Francophone Society SFGM-TC
Authors: Lea Bosdure, Jean-Hugues Dalle, Catherine Paillard, Mony Fahd, Valerie Coiteux, Nadine Petitpain, Danièle Bensoussan, Jacques-Olivier Bay, Marie Thérèse Rubio, Cecile Pochon
Journal: Blood (2020)
Predictors of Survival and Time to Progression to Myeloid Neoplasm in Patients with Clonal Cytopenias
Authors: Ahmad Nanaa, Rama Nana, Zhuoer Xie, Dragan Jevremovic, Phuong L. Nguyen, Cynthia Hengel, Susan M. Geyer, Rong He, David S. Viswanatha, Michael M. Timm, Mohamed E Salama, Min Shi, Patricia Greipp, Hassan B. Alkhateeb, William J Hogan, Mark Litzow, Mrinal M. Patnaik, Mithun Vinod Shah, Aref Al-Kali
Journal: Blood (2020)
Secretory Mucin 5AC Promotes Neoplastic Progression by Augmenting KLF4-Mediated Pancreatic Cancer Cell Stemness
Authors: Koelina Ganguly, Shiv Ram Krishn, Satyanarayana Rachagani, Rahat Jahan, Ashu Shah, Palanisamy Nallasamy, Sanchita Rauth, Pranita Atri, Jesse L. Cox, Ramesh Pothuraju, Lynette M. Smith, Sudhua Ayala, Christopher Evans, Moorthy P. Ponnusamy, Sushil Kumar, Sukhwinder Kaur, Surinder K. Batra
Journal: Cancer Research (2020)

Abstract Secreted mucin 5AC (MUC5AC) is the most abundantly overexpressed member of the mucin family during early pancreatic intraepithelial neoplasia stage I (PanIN-I) of pancreatic cancer. To comprehend the contribution of Muc5ac in pancreatic cancer pathology, we genetically ablated it in an autochthonous murine model (KrasG12D; Pdx-1cre, KC), which mirrors the early stages of pancreatic cancer development. Neoplastic onset and the PanIN lesion progression were significantly delayed in Muc5ac knockout (KrasG12D; Pdx-1 cre; Muc5ac−/−, KCM) animals with a 50% reduction in PanIN-2 and 70% reduction in PanIN-3 lesions compared with KC at 50 weeks of age. High-throughput RNA-sequencing analysis from pancreatic tissues of KCM animals revealed a significant decrease in cancer stem cell (CSC) markers Aldh1a1, Klf4, EpCAM, and CD133. Furthermore, the silencing of MUC5AC in human pancreatic cancer cells reduced their tumorigenic propensity, as indicated by a significant decline in tumor formation frequency by limiting dilution assay upon subcutaneous administration. The contribution of MUC5AC in CSC maintenance was corroborated by a significant decrease in tumor burden upon orthotopic implantation of MUC5AC-depleted pancreatic cancer cells. Mechanistically, MUC5AC potentiated oncogenic signaling through integrin αvβ5, pSrc (Y416), and pSTAT3 (Y705). Phosphorylated STAT3, in turn, upregulated Klf4 expression, thereby enriching the self-renewing CSC population. A strong positive correlation of Muc5ac with Klf4 and pSTAT3 in the PanIN lesions of KC mouse pancreas reinforces the crucial involvement of MUC5AC in bolstering the CSC-associated tumorigenic properties of Kras-induced metaplastic cells, which leads to pancreatic cancer onset and progression. Significance: This study elucidates that de novo expression of MUC5AC promotes cancer cell stemness during Kras-driven pancreatic tumorigenesis and can be targeted for development of a novel therapeutic regimen.
Greater Efficacy and Potency of Obinutuzumab Compared with Rituximab in Chronic Lymphocytic Leukemia Patients Confirmed By a Semi-Mechanistic Pharmacokinetic/Pharmacodynamic Model
Authors: Kubra Kamisoglu, Alex Phipps, Candice Jamois, Vincent Buchheit, Georgina Meneses-Lorente, Günter Fingerle-Rowson, Jonathan Wagg, Donald E Mager
Journal: Blood (2017)
Cortical Thinning and Neuropsychologic Measures Predict CD19 CAR T Cell Therapy-Associated Neurotoxicity
Authors: Agne Taraseviciute, Deepa Bhojwani, Ravi Bansal, Bradley S Peterson, Michael A Pulsipher, Alan S. Wayne, Courtney Allem, Michael Sheard, Joey Trampush
Journal: Blood (2020)
Abstract 274: Activation of CaMKII Signaling Pathway Contributes to the Pathogenesis of Genetic Hypertrophic Cardiomyopathy
Authors: Isaac Perea Gil, Nadjet Bellbachir, Alexandra A Gavidia, Jennifer Arthur, Yuan Zhang, Nirmal Vadgama, Angelos Oikonomopoulos, Santiago Roura, Joseph C Wu, Antoni Bayes-Genis, Ioannis Karakikes
Journal: Circulation Research (2020)

Background: Hypertrophic cardiomyopathy (HCM) is the most prevalent form of genetic cardiomyopathy associated with ventricular arrhythmia and sudden cardiac death. To date, several pathogenic variants of sarcomeric protein genes have been identified in genetic HCM. However, the mechanisms by which specific mutations cause the hallmark phenotypes of HCM remain largely unresolved. There is a major unmet need for a better understanding of disease mechanisms in order to predict individuals at risk for sudden cardiac death and design mechanism-based therapeutics. Methods: We modeled HCM in vitro using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from HCM patients with a history of ventricular arrhythmias and sudden cardiac death harboring a heterozygous mutation in the Tropomyosin 1 gene (TPM1, c.107 A&gt;G). We studied the functional and molecular consequences of the TPM1 mutation in iPSC-CMs to determine the molecular mechanism of HCM pathogenesis. Results: In mutant cardiomyocytes we observed impaired mechanical relaxation, aberrant intracellular calcium cycling and increased incidence of delayed after-depolarizations when compared to isogenic controls, recapitulating the HCM phenotype in vitro . Genome wide transcriptional profiling revealed a significant enrichment of genes associated with calcium dysregulation and the activation of the Calcium/Calmodulin-Dependent Protein Kinase II (CaMKII) pathway in mutant cardiomyocytes. Conversely, pharmacological inhibition of CaMKII pathway rescued the arrhythmic phenotype of mutant cardiomyocytes in vitro . Conclusions: Taken together, our data suggest a mechanistic link between the activation of CaMKII signaling pathway and the pathogenesis of sarcomeric HCM. These results provide a better understanding of the arrhythmogenic signaling pathway associated with the HCM phenotype and could potentially lead to mechanism-based targeted therapeutics for genetic HCM patients.
Abstract PO-050: Peripheral neurons invade oral squamous cell carcinoma microenvironment and drive tumorigenesis
Authors: Megan A. Atherton, Marci L. Nilsen, Nicole N. Scheff
Journal: Cancer Research (2020)

Abstract The impact of peripheral neurons on carcinogenesis is an understudied process in head and neck cancer. Peripheral nerve innervation is increased in preclinical models of oral cancer; sympathectomy resulted in smaller, less invasive cancers. Local neurotransmitter release from peripheral neurons innervating cancer has been linked to cancer growth and immune suppression. We hypothesize that local neurotransmitter release from trigeminal sensory neurons (TGNs) and sympathetic postganglionic neurons promotes cancer proliferation and suppresses the immune response. We used real-time PCR to determine RNA expression in human oral cancer cell lines and a colorimetric cell proliferation assay to quantify cancer cell growth in response to the sympathetic and sensory neurotransmitters. Oral cancer cell lines, HSC-3 and SCC-4, overexpress the norepinephrine (NE) receptor, adrenergic receptor beta 2 (ADRβ2) and sensory neurotransmitter receptors, receptor activity modifying protein1 (RAMP1) and neurokinin1 receptor (NK1R) compared to the non-tumorigenic cell line, HaCaT. Treatment with sympathetic (NE) and sensory (CGRP, substance p) neurotransmitters for 48 hours significantly increased cell proliferation in HSC-3 (&amp;gt;2-fold) and SCC-4 (&amp;gt;1.5-fold) cell lines, but had no effect on HaCaT cell proliferation. Using optical clearing and immunohistochemistry, we observed increased PGP9.5+ neuronal fiber density in the microenvironment using high-resolution microscopy in a tongue oral cancer xenograft mouse model. In vitro we measured a 44.6 ± 1.14% increase in TGN sprouting after 48-hour exposure to conditioned media from the HSC-3, compared to conditioned media from HaCaT. Lastly, HSC-3 cell culture supernatant injection (50 µl) into the tongue of C57Bl/6 female mice resulted in infiltration of CD45+ immune cells (9.10 ± 1.2 % of total live cells). Temporary nerve block with 1% bupivacaine injection into the lingual nerve prior to a 50 µl injection of HSC-3 supernatant into the tongue resulted in significantly more CD45+ immune cell infiltration (21.66 ± 3.4 %) compared to HSC-3 supernatant without pharmacologic nerve block. These results together suggest neurotransmitter-induced increase in oral cancer cell proliferation and neurotransmitter-induced suppression of the cancer-evoked immune response. Understanding the nerve-cancer interaction might improve strategies to treat head ad neck cancer by targeting peripheral neurons in the cancer microenvironment. Citation Format: Megan A. Atherton, Marci L. Nilsen, Nicole N. Scheff. Peripheral neurons invade oral squamous cell carcinoma microenvironment and drive tumorigenesis [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-050.
HookNet: Multi-resolution convolutional neural networks for semantic segmentation in histopathology whole-slide images
Authors: Mart van Rijthoven, Maschenka Balkenhol, Karina Siliņa, Jeroen van der Laak, Francesco Ciompi
Journal: Medical Image Analysis (2020)

We propose HookNet, a semantic segmentation model for histopathology whole-slide images, which combines context and details via multiple branches of encoder-decoder convolutional neural networks. Concentric patches at multiple resolutions with different fields of view, feed different branches of HookNet, and intermediate representations are combined via a hooking mechanism. We describe a framework to design and train HookNet for achieving high-resolution semantic segmentation and introduce constraints to guarantee pixel-wise alignment in feature maps during hooking. We show the advantages of using HookNet in two histopathology image segmentation tasks where tissue type prediction accuracy strongly depends on contextual information, namely (1) multi-class tissue segmentation in breast cancer and, (2) segmentation of tertiary lymphoid structures and germinal centers in lung cancer. We show the superiority of HookNet when compared with single-resolution U-Net models working at different resolutions as well as with a recently published multi-resolution model for histopathology image segmentation. We have made HookNet publicly available by releasing the source code1 as well as in the form of web-based applications2,3 based on the grand-challenge.org platform.