tbuckley/cabot-search huggingface dataset:
Blocking MAPK Activation and Immune Checkpoints Reverse Immune Dysfunction and Reduce Disease in a Mouse Model of LCH
Authors: Amel Sengal, Meryl Hahne, Jessica Velasquez, Harshal Abhyankar, Thomas Burke, Walter Olea, Robert Reyes, Brooks Scull, Camille Bigenwald, Catherine M. Bollard, Wendong Yu, Miriam Merad, Kenneth L. McClain, Carl E. Allen, Rikhia Chakraborty
Journal: Blood (2019)
R4 Rgs Subfamily Proteins Suppress Engraftment and Regulate SDF-1/CXCR4 Signaling in Human CD34+ Hematopoietic Stem/Progenitor Cells
Authors: Kathy Chan, Tsin Sik Wong, Karen Li, Xiao-Bing Zhang, Ronald Wang, King Yiu Lee, Frankie Wai Tsoi Cheng, Chi Kong Li, Kam Tong Leung
Journal: Blood (2019)
Pre-Transplant MRD Negativity Predicts Favorable Outcomes of CAR-T Therapy Followed By Haploidentical HSCT for Relapsed/Refractory Acute Lymphoblastic Leukemia: A Multi-Center Retrospective Study
Authors: Yongxian Hu, Zhao Houli, Wei Guoqing, Yi Luo, Ji Min Shi, Jing Chen, Zhang Qing, Song Xianmin, Lei Xiao, Alex Hong Chang, Didier Blaise, Mohamad Mohty, He Huang
Journal: Blood (2019)
AAV8-Specific Immune Adsorption Column: A Treatment Option for Patients with Pre-Existing Anti-AAV8 Neutralizing Antibodies
Authors: Anita Kruzik, Roland Raim, Dirk Voelkel, Markus Weiller, Werner Hoellriegl, Friedrich Scheiflinger, Hanspeter Rottensteiner, Birgit M Reipert, Maurus de la Rosa
Journal: Blood (2019)
Interleukin‐17 Inhibition in Spondyloarthritis Is Associated With Subclinical Gut Microbiome Perturbations and a Distinctive Interleukin‐25–Driven Intestinal Inflammation
Authors: Julia Manasson, David S. Wallach, Giuliana Guggino, Matthew Stapylton, Michelle H. Badri, Gary Solomon, Soumya M. Reddy, Roxana Coras, Alexander A. Aksenov, Drew R. Jones, Parvathy V. Girija, Andrea L. Neimann, Adriana Heguy, Leopoldo N. Segal, Pieter C. Dorrestein, Richard Bonneau, Monica Guma, Francesco Ciccia, Carles Ubeda, Jose C. Clemente, Jose U. Scher
Journal: Arthritis & Rheumatology (2019)

To characterize the ecological effects of biologic therapies on the gut bacterial and fungal microbiome in psoriatic arthritis (PsA)/spondyloarthritis (SpA) patients.Fecal samples from PsA/SpA patients pre- and posttreatment with tumor necrosis factor inhibitors (TNFi; n = 15) or an anti-interleukin-17A monoclonal antibody inhibitor (IL-17i; n = 14) underwent sequencing (16S ribosomal RNA, internal transcribed spacer and shotgun metagenomics) and computational microbiome analysis. Fecal levels of fatty acid metabolites and cytokines/proteins implicated in PsA/SpA pathogenesis or intestinal inflammation were correlated with sequence data. Additionally, ileal biopsies obtained from SpA patients who developed clinically overt Crohn's disease (CD) after treatment with IL-17i (n = 5) were analyzed for expression of IL-23/Th17-related cytokines, IL-25/IL-17E-producing cells, and type 2 innate lymphoid cells (ILC2s).There were significant shifts in abundance of specific taxa after treatment with IL-17i compared to TNFi, particularly Clostridiales (P = 0.016) and Candida albicans (P = 0.041). These subclinical alterations correlated with changes in bacterial community co-occurrence, metabolic pathways, IL-23/Th17-related cytokines, and various fatty acids. Ileal biopsies showed that clinically overt CD was associated with expansion of IL-25/IL-17E-producing tuft cells and ILC2s (P < 0.05), compared to pre-IL-17i treatment levels.In a subgroup of SpA patients, the initiation of IL-17A blockade correlated with features of subclinical gut inflammation and intestinal dysbiosis of certain bacterial and fungal taxa, most notably C albicans. Further, IL-17i-related CD was associated with overexpression of IL-25/IL-17E-producing tuft cells and ILC2s. These results may help to explain the potential link between inhibition of a specific IL-17 pathway and the (sub)clinical gut inflammation observed in SpA.
Natural History Study of Idiopathic Multicentric Castleman Disease Identifies Effective Treatments for a Large Proportion of Patients but Treatment-Refractory Patients Remain
Authors: Sheila K Pierson, Yue Ren, Johnson Khor, Eric Haljasmaa, Jasira Ziglar, Katherine Floess, Erin NaPier, Faizaan Akhter, Amy Y Liu, Damilola Gibson, Karan Kanhai, Rabecka Martin, Amy Chadburn, Gordan Srkalovic, Megan S. Lim, Corey Casper, Thomas S. Uldrick, Elaine S. Jaffe, Frits van Rhee, Hongzhe Lee, David C Fajgenbaum
Journal: Blood (2019)
Tuberculosis, HIV, and viral hepatitis diagnostics in eastern Europe and central Asia: high time for integrated and people-centred services
Authors: Masoud Dara, Soudeh Ehsani, Antons Mozalevskis, Elena Vovc, Daniel Simões, Ana Avellon Calvo, Jordi Casabona i Barbarà, Otar Chokoshvili, Irina Felker, Sven Hoffner, Gulmira Kalmambetova, Ecatarina Noroc, Natalia Shubladze, Alena Skrahina, Rasim Tahirli, Tengiz Tsertsvadze, Francis Drobniewski
Journal: The Lancet Infectious Diseases (2019)
Donut‐Shaped Stretchable Kirigami: Enabling Electronics to Integrate with the Deformable Muscle
Authors: Yusuke Morikawa, Shota Yamagiwa, Hirohito Sawahata, Rika Numano, Kowa Koida, Takeshi Kawano
Journal: Advanced Healthcare Materials (2019)

Electronic devices used to record biological signals are important in neuroscience, brain-machine interfaces, and medical applications. Placing electronic devices below the skin surface and recording the muscle offers accurate and robust electromyography (EMG) recordings. The device stretchability and flexibility must be similar to the tissues to achieve an intimate integration of the electronic device with the biological tissues. However, conventional elastomer-based EMG electrodes have a Young's modulus that is ≈20 times higher than that of muscle. In addition, these stretchable devices also have an issue of displacement on the tissue surface, thereby causing some challenges during accurate and robust EMG signal recordings. In general, devices with kirigami design solve the issue of the high Young's modulus of conventional EMG devices. In this study, donut-shaped kirigami bioprobes are proposed to reduce the device displacement on the muscle surface. The fabricated devices are tested on an expanding balloon and they show no significant device (microelectrode) displacement. As the package, the fabricated device is embedded in a dissolvable material-based scaffold for easy-to-use stretchable kirigami device in an animal experiment. Finally, the EMG signal recording capability and stability using the fabricated kirigami device is confirmed in in vivo experiments without significant device displacements.
TMIC-22. IDENTIFICATION OF CANCER-ASSOCIATED FIBROBLASTS IN GLIOBLASTOMA and Defining Their Protumoral Effects
Authors: Jonathan Rick, Alan Nguyen, Ankush Chandra, Harsh Wadhwa, Sumedh Shah, Lin Wang, Darryl Lau, Michael Safaee, Angel Ordaz, Garima Yagnik, Aaron Diaz, Manish Aghi
Journal: Neuro-Oncology (2019)

Abstract While cancer-associated fibroblasts (CAFs) and their pro-tumoral effects have been demonstrated in systemic cancers, CAFs had been presumed absent in glioblastoma given the lack of normal fibroblasts in the healthy brain. Here, we show that 5–26% (mean=12%) of cells in human glioblastomas express CAF markers α-SMA or PDGFR-β, morphologically resemble fibroblasts, and transcriptomically resemble by RNA-seq CAFs from other cancers. Glioblastoma CAFs were chemotactically attracted to glioblastoma-initiating stem cells (P=0.02). While glioblastoma CAFs did not affect differentiated glioblastoma cell proliferation (P=0.4), CAFs increased glioblastoma stem cell proliferation (P=0.002) and expression of glioblastoma stem cell-associated genes (P&lt; 0.001). To identify mediators of CAF/glioblastoma stem cell interactions, we created a resource of inferred crosstalk by mapping the expression of receptors to that of their cognate ligands/agonists, using our RNA-seq results from glioblastoma CAFs and stem cells, revealing PDGF-β/PDGFR and osteopontin/CD44 to mediate stem cell recruitment of CAFs and CAF enrichment of stem cells, as confirmed by blocking antibodies (P=0.02–0.03). CAFs also render the glioblastoma microenvironment more pro-tumoral by promoting M2 polarization of tumor-associated macrophages (P=0.01), an effect we found to arise from unique CAF production of the EDA splice variant of fibronectin binding toll-like receptor 4 (TLR4), a known EDA receptor expressed by macrophages (P=0.02). In patient glioblastomas, CAFs were enriched 3-fold in the subventricular zone (SVZ) (P=0.04) which houses the neural stem cells that generate glioblastoma stem cells. SVZs from epilepsy cases or autopsies of glioblastoma-containing brains without ventricular involvement lacked CAFs. Depleting CAFs in xenografts derived from neurosphere-containing glioblastoma stem cells slowed their growth in vivo (P&lt; 0.001). These findings are among the first to identify and profile glioblastoma CAFs. CAF recruitment by glioblastoma stem cells and creation of a pro-tumoral microenvironment in the perivascular niche housing glioblastoma stem cells, particularly in the SVZ, makes them an intriguing therapeutic target.
Sex Differences in Risk Factors, Clinical Presentation, Treatment and Outcomes of Patients Presenting with Acute Pulmonary Embolism
Authors: Rachel P Rosovsky, Islam Y Elgendy, Suzanne C Cannegieter, Menno V Huisman, David Jimenez, Jorge del Toro, Vladimir Rosa, Carmen Fernández-Capitán, Alessandra Bura-Riviere, Manuel Monreal
Journal: Blood (2019)
Porous poly(ε-caprolactone) implants: A novel strategy for efficient intraocular drug delivery
Authors: Raquel Boia, Paulo A.N. Dias, Joana M. Martins, Caridad Galindo-Romero, Inês D. Aires, Manuel Vidal-Sanz, Marta Agudo-Barriuso, Hermínio C. de Sousa, António Francisco Ambrósio, Mara E.M. Braga, Ana Raquel Santiago
Journal: Journal of Controlled Release (2019)

This work reports the development of porous poly (ε-caprolactone) (PCL)-based intraocular implants, prepared by green supercritical carbon dioxide (scCO2) foaming/mixing method (SFM), to produce implants that degrade faster than typical slow-degrading PCL-based implants. The higher porosities and surface areas of these implants led to faster degradation rates at in vitro accelerated alkaline conditions than low porosity/surface area implants prepared by hot melting processing. These porous implants also presented distinct (faster) release rates of a test-drug (dexamethasone). Additionally, these porous devices did not cause cell death and did not reduce the number of neurons, indicating that are not toxic to retinal cells. We further explored the impact of PCL-based implant to the retina by in vivo evaluation and histological analysis. Implants were surgically inserted in the vitreous of Wistar rats, and their presence did not change the function, structure and anatomy of the retina. These devices demonstrated a good intraocular tolerance, further confirming their viability for prolonged drug delivery applications. Further comprehensive studies based on this promising preliminary assessment and proof-of-concept could enable its future translation to clinical protective strategies for retinal diseases.
Stroke Avoidance for Children in República Dominicana (SACRED):a Prospective Trial to Reduce Stroke in Children with Sickle Cell Anemia
Authors: Luisanna Sanchez, Rosa M. Nieves, Teresa S. Latham, Adam Lane, Neelum Jeste, Gabriela S. Urcuyo, Melissa E. Berges, Carla Florencio, Carla Gonzalez, Paola Del Villar, Janet Adams, Susan Stuber, William Schultz, Rafael Mena, Russell E. Ware
Journal: Blood (2019)
PU.1 Dose-Dependently Induces Granulocyte or Macrophage Commitment by Targeting Lineage Restricted Genes and by Regulating Transcription Factors Egr2, Nab2, Cebpa and Gfi1.
Authors: Vit Pospisil, Juraj Kokavec, Pavel Burda, Nikola Curik, Arthur I. Skoultchi, Jiri Zavadil, Tomas Stopka
Journal: Blood (2007)
NCMP-12. DISSECTING THE ANTI-TUMOR IMMUNE RESPONSE IN GLIOBLASTOMA
Authors: Dan Chen
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma multiforme (GBM) is the deadliest form of brain cancer, for which there is currently no effective therapy. In clinical trials with GBM patients, immunotherapy led to an increase in the number of immune cells infiltrating the tumor, yet surprisingly not to a clinical benefit. These trials reveal the need to study how the immune system is impacted by GBM and which immune cells are the key players in the anti-tumor response. Using a GBM mouse model to guide our studies, we have found anti-CTLA4 treatment improved survival, but the efficacy of anti-CTLA4 was lost in mice that were depleted of CD4+ T cells but no other immune cells, indicating ‘helper’ CD4+ T cells were essential for anti-tumor immunity and long-term survival in GBM. Thus, it is imperative to explore the types of CD4+ T cells in these tumors helping to controlling GBM and response to anti-CTLA4. We also find some specific myeloid population is disappeared after CD4 depletion. We need to understand how the function of CD4 T cells impacts other immune cells in the context of GBM. Furthermore, the future goal of this work is to extend to characterize the immune compartment of clinical GBM, which will provide important implications for how to effectively improve current immunotherapy to overcome GBM.
Antenatal Preparation for Labour
Authors: D. C. Scott
Journal: BMJ (1964)

large amounts of " bovril," " oxo," and "virol," or spinach and lentils.One 8-oz.(227-g.)bottle of " virol " contains only 64 mg. of available iron, costing 3s.6d., com- pared with three ferrous-gluconate tablets containing 108 mg. of absorbable iron,' cost- ing less than ld.On economic grounds alone one could not justify the dietary recommendation, the efficacy of which is doubtful.Surely £1 for one's total supply of iron throughout pregnancy is a small price to pay to assure a safe haemoglobin level at term ?Indeed, Professor G. G. Lennon remarks in his book' that there is no reason why all pregnant women should not have a Hb of 100% at term if prophylactic iron is given.The other controversial point of this article is the comment about hypertension.Patients with a blood-pressure of 140/90 or over should have initial assessment to ascertain the cause-that is, chronic nephritis, coarctation of the aorta, and phaeochromocytoma, etc., careful and frequent examination and induction at the 38th-39th week, with full appreciation of the risk of intrauterine death.2Consequently, I do not think this article warrants the title " Current 'Practice " with the treatment of two disorders so out of line with current obstetric practice.-Iam, etc., Bristol 4.
Long-Term Follow-up of a Phase 1, First-in-Human Open-Label Study of LCAR-B38M, a Structurally Differentiated Chimeric Antigen Receptor T (CAR-T) Cell Therapy Targeting B-Cell Maturation Antigen (BCMA), in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM)
Authors: Bai-Yan Wang, Wan-Hong Zhao, Jie Liu, Yin-Xia Chen, Xing-Mei Cao, Yun Yang, Yi-Lin Zhang, Fang-Xia Wang, Peng-Yu Zhang, Bo Lei, Liu-Fang Gu, Jian-Li Wang, Jia-Jia Zhang, Ru Zhang, Hui Zhang, Ying Shen, Ju Bai, Yan Xu, Xu-Geng Wang, Rui-Li Zhang, Li-Li Wei, Zong-Fang Li, Gai-Xia He, Yan Geng, Qian He, Qiu-Chuan Zhuang, Frank Xiao-Hu Fan, Wang-Gang Zhang, Ai-Li He
Journal: Blood (2019)
Percutaneous transhepatic cholangiography.
Authors: G M Fraser, J G Cruickshank, C W Falconer
Journal: BMJ (1976)

shown by the experience of Dr John Paulley (20 November, p 1252) in the Ipswich District.Together with the more favoured Cambridge and Norwich Districts they combine to put the East Anglian Region on the national average.Annual differential incremental growth money, not money stolen from the London till, is surely the only real solution for the future.But we may have to await the restora- tion of the nation's finances by the International Monetary Fund and forward-looking politicians.Incidentally, have the favoured regions used their extra millions this year productively or has the money paid for infla- tion and junior doctor's pay awards ?Of course RAWP is right in wishing to equate resources with medical need.However, first they must define "need" and then show how to measure it.Then they may bring the Tablets down from the Mountain.
Significance of Modified Risk Stratification Msmart 3.0 and Autologous Stem Cell Transplantation for Patients with Newly Diagnosed Multiple Myeloma
Authors: Andrey Garifullin, Sergei Voloshin, Vasily Shuvaev, Irina Martynkevich, Elizaveta Kleina, Alexander Chechetkin, Stanislav Bessmeltcev, Anastasiya Kuzyaeva, Alexander Sсhmidt, Alexey Kuvshinov, Irina Pavlova
Journal: Blood (2019)
Altered Immunophenotypes on Leukemic and/or Monocytic Cells from Acute Myeloid Leukemia Highly Predict for Nucleophosmin Gene Mutation
Authors: Sergio Matarraz, Pilar Leoz, Xavier Calvo, Luis García Alonso, Rosa Ayala Bueno, José Ignacio Sánchez-Gallego, Neus Villamor, Enrique Colado, María Belén Vidriales, María Isabel Prieto Conde, Maria Carmen Chillon, Ramón García-Sanz, Vincent H.J. Van Der Velden, Félix López Cadenas, María Díez-Campelo, Leonor Arenillas, Sara Alonso, Ariana Fonseca, Covadonga Quirós Caso, Laura Magnano, José Antonio Garcia Vela, Carlos Fernandez, Daniela Damasceno, Andrea Mayado, Susana Barrena, Alberto Orfao
Journal: Blood (2019)
INNV-16. COMPLETE RESPONSE OF THALAMIC IDH WILDTYPE GLIOBLASTOMA AFTER PROTON THERAPY FOLLOWED BY CHEMOTHERAPY TOGETHER WITH TUMOR TREATING FIELDS
Authors: Marco Stein, Hildegard Dohmen, Bernhard Woelk, Eberhard Uhl, Alexandra Jensen
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Proton therapy is able to apply high radiation doses to the tumor while sparing healthy tissues by reducing integral dose. Tumor Treating Fields (TTFields) are low intensity (1–3 V/cm) and intermediate frequency (100–300 kHz) alternating electric fields that demonstrated significantly increased survival rates in combination with adjuvant temozolomide (TMZ) in patients with newly diagnosed glioblastoma (ndGBM). Here, we report on a patient with biopsied ndGBM IDH wildtype with complete radiological response. MATERIAL AND METHODS Brain MRI demonstrated an occlusive hydrocephalus and a ring enhancing lesion in the right posterior thalamus in a 42 year old male. After endoscopic ventriculostomy and stereotactic biopsy histopathological examination resulted in the diagnosis of a glioblastoma (WHO grade IV), IDH 1 wildtype (R132), IDH 2 wildtype (R172), HIST1H3B/C wildtype, TERT wildtype (C228 and C250), BRAF wildtype, and unmethylated MGMT promotor. The patient received definitive chemoradiation with TMZ to a total dose of 60Gy incl. proton boost of 5x2 GyRBE. TTFields therapy in combination with TMZ was initiated 4 weeks after completion of chemoradiation, TMZ maintenance was completed per protocol after 6 cycles. TTFields therapy was continued for more than 13 month and to-date the patient is still on therapy. RESULTS Current follow up time is 20 months after initial diagnosis with the patient showing a radiological complete response. In a MRI 9 months after proton therapy, partial response and perfusion restriction in the tumor area was observed. Another MRI 3 months later showed a complete response without perfusion signal in the tumor area. CONCLUSION Complete response was observed following combination treatment of chemoradiation with TMZ including proton boost, TMZ maintenance and TTFields in a patient with pathologically confirmed GBM IDH wildtype. To our knowledge, this is the first report on a ndGBM patient receiving proton therapy followed by TTFields therapy.
Effects of Proximal Tubule Shortening on Protein Excretion in a Lowe Syndrome Model
Authors: Megan L. Gliozzi, Eugenel B. Espiritu, Katherine E. Shipman, Youssef Rbaibi, Kimberly R. Long, Nairita Roy, Andrew W. Duncan, Matthew J. Lazzara, Neil A. Hukriede, Catherine J. Baty, Ora A. Weisz
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Patients with Lowe syndrome (LS) develop abnormalities in proximal tubule function that cause declining kidney function. Mutations in the OCRL gene encoding cause LS. The enzyme encoded by OCRL hydrolyzes phosphatidylinositol 4,5-bisphosphate, a lipid that regulates myriad cellular functions. The authors created a knockout model of OCRL in human proximal tubule cells and observed that loss of OCRL impairs cell proliferation and results in the accumulation of multinucleated cells. Lrp2 -positive segments of the pronephric kidney were shorter in ocrl mutant and morphant zebrafish. The authors also created a mathematic model that explains how loss of functional OCRL can lead to the kidney manifestations of LS. The authors hypothesize that impaired cell proliferation results in a shorter proximal tubule in patients with LS and that this contributes to proteinuria. Background Lowe syndrome (LS) is an X-linked recessive disorder caused by mutations in OCRL , which encodes the enzyme OCRL. Symptoms of LS include proximal tubule (PT) dysfunction typically characterized by low molecular weight proteinuria, renal tubular acidosis (RTA), aminoaciduria, and hypercalciuria. How mutant OCRL causes these symptoms isn’t clear. Methods We examined the effect of deleting OCRL on endocytic traffic and cell division in newly created human PT CRISPR/Cas9 OCRL knockout cells, multiple PT cell lines treated with OCRL -targeting siRNA, and in orcl -mutant zebrafish. Results OCRL-depleted human cells proliferated more slowly and about 10% of them were multinucleated compared with fewer than 2% of matched control cells. Heterologous expression of wild-type, but not phosphatase-deficient, OCRL prevented the accumulation of multinucleated cells after acute knockdown of OCRL but could not rescue the phenotype in stably edited knockout cell lines. Mathematic modeling confirmed that reduced PT length can account for the urinary excretion profile in LS. Both ocrl mutant zebrafish and zebrafish injected with ocrl morpholino showed truncated expression of megalin along the pronephric kidney, consistent with a shortened S1 segment. Conclusions Our data suggest a unifying model to explain how loss of OCRL results in tubular proteinuria as well as the other commonly observed renal manifestations of LS. We hypothesize that defective cell division during kidney development and/or repair compromises PT length and impairs kidney function in LS patients.
Phase 1 Dose Escalation and Expansion Study to Determine Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the BET Inhibitor FT-1101 As a Single Agent in Patients with Relapsed or Refractory Hematologic Malignancies
Authors: Manish R. Patel, Guillermo Garcia-Manero, Ronald Paquette, Shira Dinner, William B. Donnellan, Michael R. Grunwald, Maria D Ribadeneira, Patricia Schroeder, Julie Brevard, Lindsey Wilson, Jennifer Sweeney, Patrick Kelly, Jeffrey E. Lancet
Journal: Blood (2019)