tbuckley/cabot-search huggingface dataset:
Hematologic Improvement-Neutrophil and -Platelet in the MEDALIST Trial: Multilineage Data from a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Luspatercept to Treat Anemia in Patients with Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions
Authors: Guillermo Garcia-Manero, Ghulam J. Mufti, Pierre Fenaux, Rena Buckstein, Valeria Santini, María Díez-Campelo, Carlo Finelli, Mario Cazzola, Osman Ilhan, Mikkael A. Sekeres, Alan F. List, Abderrahmane Laadem, Rodrigo Ito, Jennie Zhang, Anita Rampersad, Daniel Sinsimer, Peter G. Linde, Uwe Platzbecker, Rami Komrokji
Journal: Blood (2019)
Tumor Microenvironment Molecular Signatures That Define Therapeutic Resistance in Mantle Cell Lymphoma
Authors: Krystle Nomie, Nikita Kotlov, Viktor Svekolkin, Alexander Bagaev, Qingsong Cai, Jasmine Falahat, Omar Moghrabi, Felix Frenkel, Ravshan Attaulakhanov, Angela Leeming, Dayoung Jung, Holly Hill, Kelley Paige Murfin, Zhihong Chen, Kimberly Hartig, Maria Badillo, Preetesh Jain, Liang Zhang, Michael Wang
Journal: Blood (2019)
Efficacy and Toxicity of Lenalidomide for Treatment of Chronic Lymphocytic Leukemia: A Systematic Review and Meta-Analysis
Authors: Sravanthi Kotapati, Insija Ilyas Selene, Madeeha Shafqat, Syeda Fatima Hassan, Zunairah Shah, Arshia Akbar, Owais ur Rehman, Tariq Iqtidar Sadiq Syed, Marium Ghani, Syed Maaz Abdullah, Maimoona Khan, Jemin Aby Jose, Faiz Anwer
Journal: Blood (2019)
On the Use of Information Criteria for Model Selection in Phylogenetics
Authors: Edward Susko, Andrew J Roger
Journal: Molecular Biology and Evolution (2019)

The information criteria Akaike information criterion (AIC), AICc, and Bayesian information criterion (BIC) are widely used for model selection in phylogenetics, however, their theoretical justification and performance have not been carefully examined in this setting. Here, we investigate these methods under simple and complex phylogenetic models. We show that AIC can give a biased estimate of its intended target, the expected predictive log likelihood (EPLnL) or, equivalently, expected Kullback-Leibler divergence between the estimated model and the true distribution for the data. Reasons for bias include commonly occurring issues such as small edge-lengths or, in mixture models, small weights. The use of partitioned models is another issue that can cause problems with information criteria. We show that for partitioned models, a different BIC correction is required for it to be a valid approximation to a Bayes factor. The commonly used AICc correction is not clearly defined in partitioned models and can actually create a substantial bias when the number of parameters gets large as is the case with larger trees and partitioned models. Bias-corrected cross-validation corrections are shown to provide better approximations to EPLnL than AIC. We also illustrate how EPLnL, the estimation target of AIC, can sometimes favor an incorrect model and give reasons for why selection of incorrectly under-partitioned models might be desirable in partitioned model settings.
The Efficacy of Risk Score System Establishment and Methylprednisolone Stratification Treatment for Pre-Engraftment Syndrome after Unrelated Cord Blood Transplantation: A Retrospective (development) and a Prospective (validation) Study
Authors: Xiaoyu Zhu, Jiang Zhu, Baolin Tang, Kaidi Song, Linlin Jin, Huilan Liu, Changcheng Zheng, Liangquan Geng, Xuhan Zhang, Wen Yao, Xiang Wan, Juan Tong, Guangyu Sun, Zimin Sun
Journal: Blood (2019)
Switching patients to greener inhalers could be cost effective, study indicates
Authors: Lynn Eaton
Journal: BMJ (2019)

A study by UK researchers has highlighted the potential financial advantages of using respiratory inhalers that have less global warming impacts than those commonly in use.

Their paper, published in BMJ Open ,1 examined the costs of switching to inhalers with a lower potential impact. It provided an economic and a carbon footprint analysis of current NHS prescription data in England.

As The BMJ has previously reported,2 the National Institute for Health and Care Excellence already recommends that doctors discuss the best type of asthma inhaler, given the patient’s clinical need and bearing in mind effects on the climate.

Switching …
Immune Priming with Single-Agent Nivolumab Followed By Combined Nivolumab &amp; Rituximab Is Safe and Efficacious for First-Line Treatment of Follicular Lymphoma; Interim Analysis of the '1st FLOR' Study
Authors: Allison Barraclough, Geoff Chong, Michael Gilbertson, Andrew Grigg, Leonid Churilov, Tineke Fancourt, David Ritchie, Rachel Koldej, Rishu Agarwal, Kate Manos, Charmaine Smith, Kristen Houdyk, Joanne Hawking, Eliza Hawkes
Journal: Blood (2019)
Phased Variant Enrichment for Enhanced Minimal Residual Disease Detection from Cell-Free DNA
Authors: David M. Kurtz, Joanne Soo, Stefan Alig, Lyron Co Ting Keh, Charles Macaulay, Michael C. Jin, Florian Scherer, Emily G. Hamilton, Chih Long Liu, Binbin Chen, Alexander F. M. Craig, Maximilian Diehn, Ash A. Alizadeh
Journal: Blood (2019)
Update on Risk Stratification Model of Smoldering Multiple Myeloma: A Systematic Review
Authors: Saad Ullah Malik, Ahmad Abu-Hashyeh, Muhammad Sardar, Mohammad M Alhousani, Emilia Cindy Leigh, Mohamed Suliman, Abdul Mughees Rana, Samson Teka, Eva Tackett, Faiz Anwer
Journal: Blood (2019)
RARE-10. IMPROVING CARE FOR ADULT PATIENTS WITH RARE CNS TUMORS: THE NATIONAL CANCER INSTITUTE-COMPREHENSIVE ONCOLOGY NETWORK EVALUATING RARE CNS TUMORS (NCI-CONNECT) PROGRAM AND CLINIC
Authors: Christine Siegel, Margarita Raygada, Alvina Acquaye, Sylvia Stearn, Kathleen Wall, Sonja Crandon, Kristen Stevens-Brown, Jing Wu, Liz Vera, Brett Theeler, Jennifer Reyes, Nicole Leggiero, Christine Cordova, Christine Bryla, Eric Burton, Lisa Boris, Ramya Antony, Tracy Ani, Orwa Aboud, Terri Armstrong, Mark Gilbert, Marta Penas-Prado
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND While rare cancers have provided insight into mechanisms of tumorigenesis and familial syndromes, patients with rare CNS tumors and providers face unique challenges, including diagnostic delays and errors, lack of standardized approaches to care/treatment, and limited social support. Scant data exists on the natural history, health status, and impact of these tumors on life quality. This report describes an innovative clinic designed to fulfill the mission of the NCI-CONNECT program: To advance our understanding and to improve approaches to care and treatment of rare CNS tumors. METHODS A specialized weekly clinic was established incorporating routine comprehensive analysis of tumor tissue, genetic counseling with individual pedigree assessment, group meetings with a health and wellness counselor and comprehensive clinical evaluation. Patients and caregivers both participated. Descriptive statistics report of NCI-CONNECT clinic patients from January 1-May 8, 2019 are presented. RESULTS 33 patients and 32 caregivers have participated to date, representing 6 of the 12 rare tumors studied in NCI-CONNECT: 19 ependymomas, 9 oligodendrogliomas, 2 PXAs, 1 papillary pineal tumor, 1 medulloblastoma, 1 gliosarcoma. The median time from receiving pathologic material to appointment was 22 days, with analysis including methylation and next generation sequencing testing. All 33 patients underwent genetic counseling, most (n=26) having at least ≥ 2 first- or second-degree relatives diagnosed with cancer (Germline mutations/genetic predisposition testing underway). 44 patients attended (33 with 8 repeat visits) the health and wellness group sessions, with education on coping/wellness techniques included. During this same period, 7 patients participated in a rare CNS basket trial using nivolumab. CONCLUSIONS We have developed an innovative clinic model to interrogate rare CNS tumors for therapeutic targets, understand individual risk, how the patient feels and functions and conduct clinical trials. This effort has the potential to accelerate our understanding of these rare tumors and provide guidance on care.
QOLP-29. MINDFULNESS MEDITATION PRACTICE IN MALIGNANT GLIOMA PATIENTS THROUGHOUT CONCOMITANT RADIATION AND TEMOZOLOMIDE: A FEASIBILITY STUDY
Authors: Dina Randazzo, Jenny Jackman, James Herndon, Mary Affronti, Eric Lipp, Nicole Cort, Annick Desjardins, Margaret Johnson, Daniel Landi, David Ashley, Henry Friedman, Oliver Glass, Laura Porter, Katherine Peters
Journal: Neuro-Oncology (2019)

Abstract With a bleak prognosis for malignant glioma, maintaining quality of life (QoL) and decreasing distress of the patient are important in the clinical care of the patient. Mindfulness meditation is a mind-body therapy that has been recently investigated in the oncology field as a non-pharmacological strategy to ameliorate cancer symptoms and to improve QoL. This practice has not been studied in the primary brain tumor population. We initiated a pilot study among newly diagnosed brain tumor patients with the hypothesis that mindfulness meditation practice may benefit the patient by decreasing stress and anxiety and provide a means to cope with their new diagnosis. The specific aim of this pilot study is to determine the feasibility of a mindfulness meditation program to this population during standard of care chemoradiation and to determine whether it merits additional research in a subsequent trial. The intervention consists of six weekly one hour telephone-based mindfulness sessions followed by one in- person mindfulness session consisting of: mindfulness and healing, understanding stress, abiding in kindness, working with difficult emotions, finding peace, going forward and living fully. Subjects are provided with downloadable guided meditations. We plan to enroll fifteen newly diagnosed WHO grade III or IV malignant glioma subjects prior to their 6 week chemoradiation course. We will determine the percentage of subjects approached vs enrolled, number of sessions that each subject attends, completion of study questionnaires and satisfaction of the subjects. QoL surveys include: Functional Assessment of Cancer Therapy- Brain, Functional Assessment of Cancer Therapy- Cognitive Function, Pittsburgh Sleep Quality Index, Functional Assessment of Chronic Illness Therapy-Fatigue and the Five Facet Mindfulness Questionnaire – short form. 13 subjects have been approached and 8 signed consent over a two-month period. We will provide final study results at time of presentation.
IMMU-07. CELLULAR IMMUNOTHERAPY TO OVERCOME TEMOZOLOMIDE INDUCED T CELL EXHAUSTION IN GLIOBLASTOMA
Authors: Aida Karachi, Farhad Dastmalchi, Ashley O’Malley, Megan Saia, Duane Mitchell, Maryam Rahman
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION We have previously demonstrated that standard dose (SD) temozolomide results in T cell exhaustion in glioblastoma. In this study, we hypothesized that cellular immunotherapies will prevent T cell exhaustion. We tested temozolomide treatment with adoptive T cell transfer alone, dendritic cell (DC) vaccines alone and T cell transfer in combination with DC vaccines. METHOD GL-261-gp100 tumor-bearing mice were treated with SD (50 mg/kg for 5 days) or metronomic dose (MD) (25 mg/kg for 10 days) temozolomide. CD3+ T cells were isolated from Pmel mice and infused intravenously. Antigen-specific DC vaccines (gp-100) were given intradermally at the concentration of 50×104. Peripheral blood T cell populations were evaluated by flow cytometry. IFN-gamma secretion was measured for evaluation of T cells function. Survival was compared between groups. RESULTS Survival analysis demonstrated that naïve T cell transfer alone and DC vaccine alone add no survival benefit to temozolomide treatment for tumor-bearing animals. There were no significant differences in the expression of exhaustion markers of Tim-3 and Lag-3 on T cells of animals that received a combination of activated T cells and DC vaccines in the context of temozolomide therapy compared to the animals that just received temozolomide. Combination of activated T cell transfer and DC vaccines did not increase IFN-gamma secretion from T cells compared to temozolomide treated animals. Combination of naïve T cell transfer and two DC vaccines increased IFN-gamma secretion from T cells of GL-261 gp100 tumor-bearing animals. However, naïve T cell transfer and two DC vaccines in the context of temozolomide was not potent enough to extend the survival of these tumor-bearing animals. CONCLUSION Combinatorial treatment with naïve antigen-specific T cells and three dendritic cell vaccine boosters in the context of temozolomide is a promising approach to preserve T cell function and avoid T cell exhaustion.
Knock-Ins of Type-2 Calr Mutants Cause Myeloproliferative Neoplasm (MPN)-like Hematopoiesis in Mice
Authors: Keiji Minakawa, Koki Ueda, Osamu Nakajima, Tetsuro Yokokawa, Yusuke Kinishima, Tomofumi Misaka, Kazuei Ogawa, Takayuki Ikezoe, Yasuchika Takeishi, Kazuhiko Ikeda
Journal: Blood (2019)
Cell-Free DNA Genotyping Analysis in Diffuse Large B-Cell Lymphoma; The Correlation between TP53 Gene Mutation and Cereblon Gene Mutation
Authors: Hideki Uryu, Yuko Mishima, Yuji Mishima, Masahiro Yokoyama, Noriko Nishimura, Yoshiharu Kusano, Takashi Okabe, Norihito Inoue, Takanori Fukuta, Yuko Shirouchi, Kiyohiko Hatake, Yasuhito Terui
Journal: Blood (2019)
Blood Management Strategies to Reduce Transfusions after Elective Lower-Extremity Joint Arthroplasty Surgeries: One Tertiary Care Hospital's Early Experience with an Alternative Payment Model - a Total Joint 'Bundle
Authors: Ankit J. Kansagra, Saurabh Dahiya, Chester Andrzejewski, Robert Krushell, Andrew Lehman, Jordan Greenbaum, Alice Ehresman, Paul Visintainer, Joan McGirr, Kathleen Mahoney, Darlene Cloutier, Mihaela Stefan
Journal: Blood (2016)
Bedside Optic Nerve Ultrasonography for Diagnosing Increased Intracranial Pressure
Authors: Alex Koziarz, Niv Sne, Fraser Kegel, Siddharth Nath, Jetan H. Badhiwala, Farshad Nassiri, Alireza Mansouri, Kaiyun Yang, Qi Zhou, Timothy Rice, Samir Faidi, Edward Passos, Andrew Healey, Laura Banfield, Mark Mensour, Andrew W. Kirkpatrick, Aussama Nassar, Michael G. Fehlings, Gregory W.J. Hawryluk, Saleh A. Almenawer
Journal: Annals of Internal Medicine (2019)

Background: Optic nerve ultrasonography (optic nerve sheath diameter sonography) has been proposed as a noninvasive, quick method for diagnosing increased intracranial pressure. Purpose: To examine the accuracy of optic nerve ultrasonography for diagnosing increased intracranial pressure in children and adults. Data Sources: 13 databases from inception through May 2019, reference lists, and meeting proceedings. Study Selection: Prospective optic nerve ultrasonography diagnostic accuracy studies, published in any language, involving any age group or reference standard. Data Extraction: 3 reviewers independently abstracted data and performed quality assessment. Data Synthesis: Of 71 eligible studies involving 4551 patients, 61 included adults, and 35 were rated as having low risk of bias. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of optic nerve ultrasonography in patients with traumatic brain injury were 97% (95% CI, 92% to 99%), 86% (CI, 74% to 93%), 6.93 (CI, 3.55 to 13.54), and 0.04 (CI, 0.02 to 0.10), respectively. Respective estimates in patients with nontraumatic brain injury were 92% (CI, 86% to 96%), 86% (CI, 77% to 92%), 6.39 (CI, 3.77 to 10.84), and 0.09 (CI, 0.05 to 0.17). Accuracy estimates were similar among studies stratified by patient age, operator specialty and training level, reference standard, sonographer blinding status, and cutoff value. The optimal cutoff for optic nerve sheath dilatation on ultrasonography was 5.0 mm. Limitation: Small studies, imprecise summary estimates, possible publication bias, and no evaluation of effect on clinical outcomes. Conclusion: Optic nerve ultrasonography can help diagnose increased intracranial pressure. A normal sheath diameter measurement has high sensitivity and a low negative likelihood ratio that may rule out increased intracranial pressure, whereas an elevated measurement, characterized by a high specificity and positive likelihood ratio, may indicate increased intracranial pressure and the need for additional confirmatory tests. Primary Funding Source: None. (PROSPERO: CRD42017055485)
CDK8 Inhibitors Induce Transcriptional Reprogramming of AML Cells Associated with Differentiation
Authors: Milena Mazan, Marion Chapellier, Marcus Järås, Michal Mikula, Eliza Majewska, Katarzyna Wiklik, Michal Combik, Aniela Golas, Magdalena Masiejczyk, Elzbieta Fiedor, Federico Malusa, Przemyslaw Juszczynski, Magdalena Cybulska, Maciej Mikulski, Jerzy Ostrowski, Pawel Chrom, Krzysztof Brzózka, Tomasz Rzymski
Journal: Blood (2019)
I-Care for MDS: Development of Guidelines-Based Indicators for Appropriate Care in Adult Patients with Myelodysplastic Syndromes
Authors: Kristina Stojkov, Tobias Silzle, Georg Stussi, David Schwappach, Juerg Bernhard, David Bowen, Jaroslav Cermak, Avinash G. Dinmohamed, Corien Eeltink, Sabrina Eggmann, Pierre Fenaux, Ulrich Germing, Manuel Haschke, Eva Hellstrom Lindberg, Monika Heger, Arjan A. Van de Loosdrecht, Jakob R. Passweg, Michael Pfeilstocker, Uwe Platzbecker, Luca Malcovati, Antonio Medina De Almeida, Moshe Mittelman, Christine Morgenthaler, David P. Steensma, Valeria Santini, Reinhard Stauder, Argiris Symeonidis, Saemi Schaer, Charlotte Maddox, Theo M de Witte, Julia Bohlius, Nicolas Bonadies
Journal: Blood (2019)
Prophylactic <i>In Vivo</i> Hematopoietic Stem Cell Gene Therapy with an Immune Checkpoint Inhibitor Reverses Tumor Growth in Syngeneic Mouse Tumor Models
Authors: Chang Li, Meredith M. Course, Iain A. McNeish, Charles W. Drescher, Paul N. Valdmanis, André Lieber
Journal: Cancer Research (2019)

Population-wide testing for cancer-associated mutations has established that more than one-fifth of ovarian and breast carcinomas are associated with inherited risk. Salpingo-oophorectomy and/or mastectomy are currently the only effective options offered to women with high-risk germline mutations. Our goal here is to develop a long-lasting approach that provides immunoprophylaxis for mutation carriers. Our approach leverages the fact that at early stages, tumors recruit hematopoietic stem/progenitor cells (HSPC) from the bone marrow and differentiate them into tumor-supporting cells. We developed a technically simple technology to genetically modify HSPCs in vivo. The technology involves HSPC mobilization and intravenous injection of an integrating HDAd5/35++ vector. In vivo HSPC transduction with a GFP-expressing vector and subsequent implantation of syngeneic tumor cells showed >80% GFP marking in tumor-infiltrating leukocytes. To control expression of transgenes, we developed a miRNA regulation system that is activated only when HSPCs are recruited to and differentiated by the tumor. We tested our approach using the immune checkpoint inhibitor anti-PD-L1-γ1 as an effector gene. In in vivo HSPC-transduced mice with implanted mouse mammary carcinoma (MMC) tumors, after initial tumor growth, tumors regressed and did not recur. Conventional treatment with an anti-PD-L1 mAb had no significant antitumor effect, indicating that early, self-activating expression of anti-PD-L1-γ1 can overcome the immunosuppressive environment in MMC tumors. The efficacy and safety of this approach was further validated in an ovarian cancer model with typical germline mutations (ID8 p53-/- brca2-/-), both in a prophylactic and therapeutic setting. This HSPC gene therapy approach has potential for clinical translation. SIGNIFICANCE: Considering the limited prophylactic options that are currently offered to women with high-risk germ-line mutations, the in vivo HSPC gene therapy approach is a promising strategy that addresses a major medical problem.
Initial Treatment Patterns and Survival Outcomes of Mantle Cell Lymphoma Patients in China in the Rituximab Era
Authors: Yun Li, Meng Wu, Huiqiang Huang, Wei Xu, Haiwen Huang, Weili Zhao, Yanyan Wang, Shuo Liu, Pengpeng Xu, Zhengming Chen, Yuqin Song, Jia Ruan, Depei Wu
Journal: Blood (2019)
Pomalidomide, Cyclophosphamide, and Dexamethasone for Elderly, Transplant-Ineligible Patients with Relapsed and/or Refractory Multiple Myeloma Who Had Failed Treatment with Lenalidomide and Bortezomib: A Study of the Korean Multiple Myeloma Working Party (KMMWP-164 study)
Authors: Ho Sup Lee, Chang-Ki Min, Kihyun Kim, Seok Jin Kim, Je-Jung Lee, Inho Kim, Sung-Soo Yoon, Jin Seok Kim, Hyeon-Seok Eom, Dok Hyun Yoon, Cheolwon Suh, Ho-Jin Shin, Yeung-Chul Mun, Min Kyoung Kim, Sung-Nam Lim, Chul Won Choi, Hye Jin Kang
Journal: Blood (2019)
A Gain of Function Mutation in the NSD2 Histone Methyltransferase Drives Glucocorticoid Resistance Via Blocking Receptor Auto-Induction and BIM/Bmf Expression in ALL
Authors: Jianping Li, Catalina Troche, Julia Hlavka Zhang, Jonathan Shrimp, Jacob S. Roth, Duohui Jing, Alok Swaroop, Marta Kulis, Jon Oyer, Christine Will, Daphne Dupere-Richer, Alberto Riva, Crissandra Pipe, Amin Sobn, Sharon Norton, Richard Lynn Bennett, Min Shen, Matthew D. Hall, Richard B. Lock, Jonathan D. Licht
Journal: Blood (2019)
Single-Cell RNA Sequencing Reveals a Distinct Transcriptome Signature of Hematopoiesis in GATA2 Deficiency
Authors: Zhijie Wu, Shouguo Gao, Sachiko Kajigaya, Jinguo Chen, Rongye Shi, Carrie Diamond, Cindy Palmer, Amy P. Hsu, Katherine R. Calvo, Dennis D. Hickstein, Steven M. Holland, Neal S. Young
Journal: Blood (2019)
Abnormal neurovascular coupling as a cause of excess cerebral vasodilation in familial migraine
Authors: Christian Staehr, Rajkumar Rajanathan, Dmitry D Postnov, Lise Hangaard, Elena V Bouzinova, Karin Lykke-Hartmann, Flemming W Bach, Shaun L Sandow, Christian Aalkjaer, Vladimir V Matchkov
Journal: Cardiovascular Research (2019)

Abstract Aims Acute migraine attack in familial hemiplegic migraine type 2 (FHM2) patients is characterized by sequential hypo- and hyperperfusion. FHM2 is associated with mutations in the Na, K-ATPase α2 isoform. Heterozygous mice bearing one of these mutations (α2+/G301R mice) were shown to have elevated cerebrovascular tone and, thus, hypoperfusion that might lead to elevated concentrations of local metabolites. We hypothesize that these α2+/G301R mice also have increased cerebrovascular hyperaemic responses to these local metabolites leading to hyperperfusion in the affected part of the brain. Methods and results Neurovascular coupling was compared in α2+/G301R and matching wild-type (WT) mice using Laser Speckle Contrast Imaging. In brain slices, parenchymal arteriole diameter and intracellular calcium changes in neuronal tissue, astrocytic endfeet, and smooth muscle cells in response to neuronal excitation were assessed. Wall tension and smooth muscle membrane potential were measured in isolated middle cerebral arteries. Quantitative polymerase chain reaction, western blot, and immunohistochemistry were used to assess the molecular background underlying the functional changes. Whisker stimulation induced larger increase in blood perfusion, i.e. hyperaemic response, of the somatosensory cortex of α2+/G301R than WT mice. Neuronal excitation was associated with larger parenchymal arteriole dilation in brain slices from α2+/G301R than WT mice. These hyperaemic responses in vivo and ex vivo were inhibited by BaCl2, suggesting involvement of inward-rectifying K+ channels (Kir). Relaxation to elevated bath K+ was larger in arteries from α2+/G301R compared to WT mice. This difference was endothelium-dependent. Endothelial Kir2.1 channel expression was higher in arteries from α2+/G301R mice. No sex difference in functional responses and Kir2.1 expression was found. Conclusion This study suggests that an abnormally high cerebrovascular hyperaemic response in α2+/G301R mice is a result of increased endothelial Kir2.1 channel expression. This may be initiated by vasospasm-induced accumulation of local metabolites and underlie the hyperperfusion seen in FHM2 patients during migraine attack.