tbuckley/cabot-search huggingface dataset:
TORSION OF THE GALL BLADDER
Authors: L. R. Fifield
Journal: BMJ (1925)

TORSION of the gall bladder is a very rare condition, and in consequence I report the following case.A married woman, a-ged 54, with six children, whilst taking tea on February 17th, was seized with severe pain in the right upper abdomen.She vomited freq,uently bright green bile, and the pain and vomiting continued until the morning of February 19th, when she was admitted to the London Hospital.She had not previously had similar pain, nor flatulent dyspepsia, jaundice, or any abdominal condition, although, until seven years ago, she was alleged to have suffered from periodic " bilious attacks," con- sisting of headache, slight sickness, but no paini, lasting for about a day.She was always constipated.
CSIG-03. STAT3-BASED PATIENT STRATIFICATION IN PRECISION NEURO-ONCOLOGY
Authors: Melanie Tan, Edwin Sandanaraj, Yuk-Kien Chong, See-Wee Lim, Lynnette Koh, Wai-Hoe Ng, Nguan-Soon Tan, Patrick Tan, Beng-Ti Ang, Carol Tang
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma (GBM) displays both spatial and temporal heterogeneity, whereupon mesenchymal tumors fare more poorly than the proneural molecular subtype. STAT3 was selected because its activation preceeds the proneural-mesenchymal transition. We first defined a STAT3 gene signature that stratified GBM patients into STAT3-high and -low cohorts. STAT3 inhibitor treatment selectively mitigated STAT3-high cell viability and tumorigenicity in orthotopic mouse xenograft models. In addition, we elucidated the mechanism underlying resistance in STAT3-low cells by combining STAT3 signature analysis with kinome screen data on STAT3 inhibitor-treated cells, allowing us to draw connections between kinases affected by STAT3 inhibitors, their associated transcription factors and target genes. As such, we show that dual inhibition of IGF-1R and STAT3 sensitized STAT3-low cells and improved survival in mice. Our study emphasizes the clinical implications of molecular subtype switching and demonstrates the importance of serially profiling GBM tumors upon recurrence so as to facilitate effective therapy.
Leukemic Stem Cells Persistence Measured By Multiparametric Flow Cytometry Is a Biomarker of Poor Prognosis in Adult Patients with Acute Myeloid Leukemia
Authors: Francesco Buccisano, Raffaele Palmieri, Maria Irno Consalvo, Alfonso Piciocchi, Luca Maurillo, Maria Ilaria Del Principe, Valentina Arena, Stefano Soddu, Ambra Di Veroli, Giovangiacinto Paterno, Eleonora De Bellis, Daniela Fraboni, Consuelo Conti, Maria Teresa Voso, William Arcese, Adriano Venditti
Journal: Blood (2019)
Pneumocystis carinii Pneumonia
Authors: B. H. Hyun
Journal: JAMA (1975)

<h3>To the Editor.—</h3> The recent report by Redman (230:1561, 1974) concerning<i>Pneumocystis carinii</i>pneumonia in an adopted Vietnamese infant was of interest to us, as we previously reported the first such case in an adopted Korean infant inThe Journal.<sup>1</sup>In both cases the infants were born in Asian countries afflicted by recent wars and cared for in orphanages until their adoption by American parents, and the symptoms of the disease became apparent on arrival in the United States. The infant we reported had severe clinical manifestations, and death resulted from respiratory failure on the 19th hospital day. The infant reported by Redman also had a fulminant course but recovered, probably because of effective therapy consisting of pentamidine isethionate and leucovorin calcium. The importance of epidemiological surveillance of American adopted orphans for pneumocystosis, as urged by Eidelman et al,<sup>2</sup>was also mentioned in our previous publication, in which
A Test to Quantify NOTCH Pathway Activity in T Cell Acute Lymphoblastic Leukemia Patients
Authors: Kirsten Canté-Barrett, Laurent Holtzer, Henk van Ooijen, Rico Hagelaar, Valentina Cordo', Wim Verhaegh, Anja van de Stolpe, Jules P.P. Meijerink
Journal: Blood (2019)
RBTT-12. A PHASE I STUDY OF EGFRVIII-DIRECTED CAR T CELLS COMBINED WITH PD-1 INHIBITION IN PATIENTS WITH NEWLY, DIAGNOSED, MGMT-UNMETHYLATED GLIOBLASTOMA: TRIAL IN PROGRESS
Authors: Stephen Bagley, Arati Desai, Zev Binder, MacLean Nasrallah, Wei-Ting Hwang, Eileen Maloney-Wilensky, Timothy Prior, Steven Brem, Donald O’Rourke
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND This study builds on the results of the University of Pennsylvania sponsored phase I study of a single peripheral infusion of chimeric antigen receptor (CAR) T cells targeting epidermal growth factor receptor variant III (EGFRvIII) in recurrent glioblastoma (GBM) (NCT02209376). A dose of 5x108 CART-EGFRvIII cells was safe, and the cells were able to expand in the host and reach the GBM tumor in the brain. In addition, there was no cross-reactivity of CART-EGFRvIII cells with wild-type EGFR normally expressed by human tissues. Some patients required tumor resection after CAR T cell infusion. In situ evaluation of the tumor microenvironment demonstrated increased and robust expression of inhibitory molecules, such as programmed death-ligand 1 (PD-L1), compared to pre–CART-EGFRvIII tumor specimens. Therefore, we hypothesized that using a combination of CART-EGFRvIII cells and a PD-1 inhibitor would improve the outcome of the treatment. METHODS This single-center study (NCT03726515) has a single-arm, open-label, phase 1 design and will enroll 7 patients with newly diagnosed, O6-methylguanine-methyltransferase (MGMT)-unmethylated, EGFRvIII+ GBM. Following maximal safe tumor resection, patients receive a short course of adjuvant radiation with a total dose of 40 Gy administered in 15 fractions. Peripheral IV infusions of 2x108 CART-EGFRvIII cells and 200mg pembrolizumab begin 2–3 weeks after completing radiation therapy. Thereafter, subjects receive CART-EGFRvIII cells + pembrolizumab in 3-week cycles for up to 3 infusions of CART-EGFRvIII cells and 4 infusions of pembrolizumab. The primary endpoint of the study is the safety and tolerability of administering multiple infusions of CART-EGFRvIII cells in combination with pembrolizumab, as measured by the occurrence of study-related adverse events. Secondary endpoints include overall survival, progression-free survival, and objective response rate. PROGRESS: At 5 June 2019, 2 patients have been enrolled and treated on study.
Mechanistic Characterization of Tafasitamab-Mediated Antibody-Dependent Cellular Phagocytosis Alone or in Combination with Lenalidomide
Authors: Dimitrios Mougiakakos, Simon Voelkl, Christian Bach, Andrej Stoll, Katrin Bitterer, Fabian Beier, Jan Endell, Rainer Boxhammer, Jörg Thomas Bittenbring, Andreas Mackensen, Heiko Bruns
Journal: Blood (2019)
Comparable Outcomes between Unrelated Donor (8/8 or 7/8 matched) and Haploidentical Donor for Allogeneic Stem Cell Transplantation in Adult Patients with Severe Aplastic Anemia
Authors: Jee Yon Shin, Sung-Soo Park, Gi June Min, Silvia Park, Sung-Eun Lee, Jae-Ho Yoon, Seung-Hwan Shin, Sung-Eun Lee, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Hee-Je Kim, Seok-Goo Cho, Jong-Wook Lee
Journal: Blood (2019)
Immunophenotyping and Function of Peripheral Blood Mononuclear Cells in Patients Undergoing Unrelated Allogeneic Transplantation with Post-Transplantation Cyclophosphamide in Combination with ATG Anti-Graft Versus Host Disease Prophylaxis
Authors: Katia Beider, Valeria Voevoda, Noga Shem-Tov, Ronit Yerushalmi, Ivetta Danilesko, Ania Hava Grushchenko-Polaq, Olivia Devillers, Idit Wolf, Olga Ostrovsky, Avichai Shimoni, Arnon Nagler
Journal: Blood (2019)
Epidemiologic Characteristics of Multimorbidity and Sociodemographic Factors Associated With Multimorbidity in a Rapidly Aging Asian Country
Authors: Lian Leng Low, Yu Heng Kwan, Michelle Shi Min Ko, Cheng Teng Yeam, Vivian Shu Yi Lee, Wee Boon Tan, Julian Thumboo
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Multimorbidity is a growing health care problem in aging societies and is strongly associated with epidemiologic characteristics and sociodemographic factors. Knowledge of these associations is important for the design of effective preventive and management strategies. <h3>Objectives</h3> To determine the association between multimorbidity and sociodemographic factors (age, socioeconomic status [SES], sex, and race/ethnicity) and the association between mental health diseases and physical diseases, as well as their implications for the types and costs of health care use. <h3>Design, Setting, and Participants</h3> This population-based cross-sectional study used deidentified Singapore Eastern Regional Health System data collected between January 1, 2012, and December 31, 2016. Patients who were alive as of January 1, 2016, and residing in the Regional Health System region in 2016 (N = 1 181 024) were included. Patients who had no year of birth records (n = 573), were born in 2017 (n = 93), or died before January 1, 2016 (n = 47 322), were excluded. <h3>Main Outcomes and Measures</h3> Multimorbidity, age, sex, SES, mental health, race/ethnicity, and health care use. <h3>Results</h3> In the study population of 1 181 024 individuals, the mean (SD) age was 39.6 (22.1) years, 51.2% were women, 70.1% were Chinese, 7.1% were Indian, 13.5% were Malayan, and 9.3% were other races/ethnicities. Multimorbidity, present in 26.2% of the population, was more prevalent in female (26.8%; 95% CI, 26.7%-26.9%) than in male (25.6%; 95% CI, 25.5%-25.7%) patients and among patients with low SES (41.6%) than those with high SES (20.1%). Mental health diseases were significantly more prevalent among individuals with low SES (5.2%; 95% CI, 5.1%-5.2%) than high SES (2.1%; 95% CI, 2.0%-2.1%;<i>P</i> &lt; .001). The 3 most prevalent disease combinations were chronic kidney disease and hypertension, chronic kidney disease and lipid disorders, and hypertension and lipid disorders. Although chronic kidney disease, hypertension, lipid disorders, and type 1 and/or type 2 diabetes–related diseases had a low cost per capita, the large number of patients with these conditions caused the overall proportion of the cost incurred by health care use to be more than twice that incurred in other diseases. <h3>Conclusions and Relevance</h3> These findings emphasize the association between multimorbidity and sociodemographic factors such as increasing age, lower SES, female sex, and increasing number of mental disorders. Health care policies need to take sociodemographic factors into account when tackling multimorbidity in a population.
Superoxide Drives PI3 Kinase Mediated Mitochondria Transfer from the Bone Marrow Microenvironment to Hematopoietic Stem Cells in Response to Salmonella Typhimurium
Authors: Jayna J Mistry, Christopher R Marlein, Jamie A Moore, Charlotte Hellmich, Iain Macauley, Naiara Beraza, Yu Sun, Adam Morfakis, Angela Patterson, Rebecca H Horton, Devina Divekar, Christopher J Morris, Anna Haestier, Federica Di Palma, Kristian M Bowles, Stuart A Rushworth
Journal: Blood (2019)
ANGI-08. AN ANNEXIN A2-REGULATED PHENOTYPIC SHIFT IN GLIOMA
Authors: Yuji Matsumoto, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Yoshihiro Otani, Atsushi Fujimura, Kentaro Fujii, Yosuke Shimazu, Yusuke Tomita, Yasuhiko Hattori, Atsuhito Uneda, Nobushige Tsuboi, Keisuke Kaneda, Keigo Makino, Isao Date
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Malignant glioma has a poor prognosis and is characterized by excessive proliferation, invasion, and angiogenesis. Previously, we established subclones of glioma cell lines with different invasive phenotypes to investigate the mechanisms of invasion in this malignancy. That study revealed annexin A2 (ANXA2) as an activator of angiogenesis and perivascular invasion. Here, we investigated the molecular mechanism of the phenotypic shift in glioma that is induced by ANXA2. METHODS We identified ANXA2 target genes using microarray analyses of our four established cell lines and RNA-seq data from the IVY Glioblastoma Atlas Project. Co-expression was then confirmed in human glioma cells. Additionally, qRT-PCR, immunoblotting, invasion assays, proliferation assays, and tube formation assays were performed to uncover the specific roles of these angiogenic invasion-related genes. Furthermore, we examined survival times and phenotypic shifts in vivo. RESULTS We identified oncostatin M receptor (OSMR) as an ANXA2-target gene using microarray and RNA-seq, and confirmed its expression correlated with ANXA2 in glioma cells. ANXA2-overexpressing glioma cells showed enhanced OSMR expression and STAT3 phosphorylation, while STAT3 knockdown reduced OSMR expression. When ANXA2 was overexpressed in glioma cells, invasion, angiogenesis, proliferation, and epithelial-mesenchymal transition were promoted; however, silencing OSMR attenuated the ANXA2-induced phenotypic shift. In vivo, ANXA2-overexpressing glioma cells shortened the survival time of tumor-bearing mice, whereas OSMR knockdown increased survival times. CONCLUSIONS We analyzed genes whose expression was regulated by ANXA2 in glioma using invasive glioma models. Through this analysis, we identified that ANXA2 and OSMR regulate a phenotypic shift, suggesting that OSMR could be a promising target to treat and prevent glioma invasion.
Next Generation Sequencing and Microrna Assay in a Cohort of Patients Affected By Myelodysplastic Syndromes. an Analysis of Clinical and Genotypic Features
Authors: Daniele Avenoso, Margherita Squillario, Annalisa Barla, Alessandro Verri, Enrico Carminati, Clara Nurra, Elisabetta Todisco, Federica Gigli, Giuliana Gregato, Claudia Poletti, Francesco Bertolini, Ghulam J. Mufti, Mili Shah, Maurizio Miglino
Journal: Blood (2019)
EXTH-45. THERAPEUTIC EFFICACY OF MUTANT ISOCITRATE DEHYDROGENASE 1 (IDH1) INHIBITOR SYC-435 WITH STANDARD THERAPY IN PATIENT-DERIVED IDH1 MUTANT GLIOMA XENOGRAFT MOUSE MODELS
Authors: Mari Kogiso, Lin Qi, Huiyuan Zhang, Frank Braun, Yuchen Du, Lei Huang, Lei Guo, Yulun Huang, Holly B Lindsay, Sibo Zhao, Sarah Injac, Patricia Baxter, Jack Su, Laszlo Perlaky, Williams Parsons, Murali Chintagumpala, Adesina Adekunle, Jialiang Wang, Yongcheng Song, Xiao-Nan Li
Journal: Neuro-Oncology (2019)

Abstract Mutation in isocitrate dehydrogenase 1 (IDH1) occurs in &gt;70% of WHO grade II/III astrocytomas, oligodendrogliomas and secondary glioblastoma. The mutant enzyme catalyzes the reduction of α-ketoglutaric acid to D-2-hydroxyglutaric acid, leading to cancer initiation. In this study, we examined therapeutic efficacy of SYC-435 (1-hydroxypyridin-2-one), a newly developed mutant IDH1inhibitor, in IDH1 mutant gliomas. IDH1 R132H mutation (homozygous) was detected in BT142 anaplastic oligoastrocytoma (AOA) and R132C mutation (mutant allele frequency 39–50%) in V0914AOA by pyrosequencing. Suppression of cell growth by SYC-435 was observed with more sensitive of mutant over wild-type IDH1. Patient-derived orthotopic xenograft mouse models of BT142AOA and V0914AOA were treated with vehicle, SYC-435 (15 mg/kg/day x 28 days), temozolomide (50 mg/kg/day x 5 days)/fractionated radiation (2 Gy/day x 5 days) (standard therapy), and SYC-435/standard therapy starting 2 weeks after intracranial tumor implantation. Log rank analysis showed SYC-435 alone did not alter survival times. Although standard therapy significantly prolonged survival times in both models (P&lt; 0.0005), SYC-435/standard therapy further extended survival times (P&lt; 0.05) in V0914AOA and exhibited similar trend in BT142AOA. Elevation of 2-HG/α-KG ratio and methylation of H3K4/H3K9 in V0914AOA tumor compared to wild-type model was detected at the end of treatments. SYC-435 with/without standard therapy tended to reduce 2-HG/α-KG ratio and dramatically reduced methylation of H3K4/H3K9. RNA-seq analysis showed sirtuin signaling pathway, mitochondrial dysfunction and oxidative phosphorylation pathways with mitochondrial DNA (mtDNA) encoded molecules were highly affected by all treatments. However, mtDNA regulation did not correlate to survival benefits. In conclusion, SYC-435 possesses anti-tumor effects that are more sensitive in IDH1 mutant gliomas and generated strong synergistic activities with standard therapies for survival benefits with reduced methylation of H3K4/H3K9. Treatments significantly affected mtDNA but significance to survival benefits remains to be elucidated. Our data support the clinical testing of SYC-435 in patients with IDH1 mutant glioma.
Bell's palsy
Authors: Jo Piercy
Journal: BMJ (2005)

A 32 year old man presents to you with sudden onset of weakness on the left side of his face. He also says that he is unable to close his left eye. He is otherwise well and last saw a doctor five years ago. He is anxious and thinks he has had a stroke.

Associated symptoms —Patients with Bell's palsy commonly feel pain in or behind the ear. Numbness can occur on the affected side of the face. Loss of taste on the ipsilateral anterior two thirds of the tongue is common. Ask about associated hyperacusis and any presence of rash that may indicate herpes zoster.

Aetiology —Ask about recent viral infection and recent immunisation. The causes of Bell's palsy are unknown, but the possibilities include viral infection, heredity, autoimmune or vascular ischaemia, of which the most likely cause is viral.

Incidence —Bell's palsy is commonest in the age group 10 …
Graft Versus Host Disease Leads to Elimination of Tissue-Resident Innate Lymphoid Cells Following Experimental and Clinical Allogeneic Transplantation
Authors: Paola Vinci, Elena Garcia-Martinez, Margaret H. O'Connor, Anastasiya Egorova, Jason Kuttiyara, Viktor Arnhold, Doris M Ponce, Alan M. Hanash
Journal: Blood (2019)
Ripk3 Signaling Regulates Hematopoietic Stem Cell Number and Function during Stress
Authors: Lei Zhang, Huacheng Luo, Jing Li, Hong-Min Ni, Mark Sellin, Feng Zhang, Jun Zhang, Peter Breslin, Wei Wei, William Small, Wen-Xin Ding, Suming Huang, Jiwang Zhang
Journal: Blood (2019)
T Cells Educated By DC/AML Fusions in the Context of 4-1BB Costimulation As a Potent Strategy for Adoptive Cellular Therapy
Authors: Jessica Liegel, Dina Stroopinsky, Haider Ghiasuddin, Adam Morin, Marzia Capelletti, Shira Orr, Maryam Rahimian, Lina Bisharat, Shufen Meng, Myrna Nahas, Matthew Weinstock, Donald Kufe, Jacalyn Rosenblatt, David E. Avigan
Journal: Blood (2019)
Dynamic remodeling of a basolateral-to-central amygdala glutamatergic circuit across fear states
Authors: Nolan D. Hartley, Andrew D. Gaulden, Rita Báldi, Nathan D. Winters, Gregory J. Salimando, Luis Eduardo Rosas-Vidal, Alexis Jameson, Danny G. Winder, Sachin Patel
Journal: Nature Neuroscience (2019)
T Cell Immunity Toward Viral- and Tumor-Antigens Is Preserved in MDS Patients
Authors: Hussein Hamad, Wingchi K Leung, Spyridoula Vasileiou, Shivani Mukhi, Quillan Huang, George Carrum, Carlos A. Ramos, Rammurti Kamble, LaQuisa C. Hill, Ann M. Leen, Premal Lulla
Journal: Blood (2019)
Post-Transplant Flow Cytometry MRD Predicts Relapse in a Real World AML Cohort
Authors: Henry Wood, Katy Sanchez, Victoria Potter, Austin Kulasekararaj, Hugues de Lavallade, Deborah Yallop, Shireen Kassam, Robin M. Ireland, Antonio Pagliuca, Ghulam J. Mufti, Alan Dunlop
Journal: Blood (2019)
Novel risk genes and mechanisms implicated by exome sequencing of 2572 individuals with pulmonary arterial hypertension
Authors: Na Zhu, Michael W. Pauciulo, Carrie L. Welch, Katie A. Lutz, Anna W. Coleman, Claudia Gonzaga-Jauregui, Jiayao Wang, Joseph M. Grimes, Lisa J. Martin, Hua He, Pah Biobank Enrolling Centers’ Investigators, Yufeng Shen, Wendy K. Chung, William C. Nichols
Journal: Genome Medicine (2019)

Group 1 pulmonary arterial hypertension (PAH) is a rare disease with high mortality despite recent therapeutic advances. Pathogenic remodeling of pulmonary arterioles leads to increased pulmonary pressures, right ventricular hypertrophy, and heart failure. Mutations in bone morphogenetic protein receptor type 2 and other risk genes predispose to disease, but the vast majority of non-familial cases remain genetically undefined.To identify new risk genes, we performed exome sequencing in a large cohort from the National Biological Sample and Data Repository for PAH (PAH Biobank, n = 2572). We then carried out rare deleterious variant identification followed by case-control gene-based association analyses. To control for population structure, only unrelated European cases (n = 1832) and controls (n = 12,771) were used in association tests. Empirical p values were determined by permutation analyses, and the threshold for significance defined by Bonferroni's correction for multiple testing.Tissue kallikrein 1 (KLK1) and gamma glutamyl carboxylase (GGCX) were identified as new candidate risk genes for idiopathic PAH (IPAH) with genome-wide significance. We note that variant carriers had later mean age of onset and relatively moderate disease phenotypes compared to bone morphogenetic receptor type 2 variant carriers. We also confirmed the genome-wide association of recently reported growth differentiation factor (GDF2) with IPAH and further implicate T-box 4 (TBX4) with child-onset PAH.We report robust association of novel genes KLK1 and GGCX with IPAH, accounting for ~ 0.4% and 0.9% of PAH Biobank cases, respectively. Both genes play important roles in vascular hemodynamics and inflammation but have not been implicated in PAH previously. These data suggest new genes, pathogenic mechanisms, and therapeutic targets for this lethal vasculopathy.
Breast cancer patients' perceived quality of care: The importance of trust and communication
Authors: R. Franco, K. P. Joseph, K. Fei, N. Bickell
Journal: Journal of Clinical Oncology (2009)

6554 Background: As insurers consider paying for performance and quality measures grow in importance, factors that affect patients’ perceived quality of cancer care matter. We undertook this study to assess predictors of women's ratings of the quality of their breast cancer care. Methods: 210 of 300 eligible women with stage I or II breast cancer at 1 of 8 participating NYC hospitals were enrolled in our survey: 43 (20%) were African-American (AA), 85 (40%) were white, and 63 (30%) were Hispanic and 19 (9%) were other races. All patients were telephone-surveyed to assess care experiences, knowledge, attitudes &amp; beliefs about breast cancer and its treatment. Trust is based on a validated instrument and calibrated to a 100 point scale (Cronbach α = 0.73). A scale of 5 items assessing physician communication was created and calibrated to100 points (Cronbach α = 0.83). Results: Only 55% of women rated their quality of cancer care as excellent. Compared to women who did not rate their care as excellent, those who did had greater trust in their physician (p &lt; 0.0001), better communication with their physician (p &lt; 0.0001), indicated that were treated well by their physicians’ office staff (p = 0.01), and knew which physician to ask when they had questions (p = 0.0001); age, education &amp; income were not significantly related to patient report of excellent care. AA women were least likely to rate their care as excellent (p = 0.004). AA women had lower levels of trust in their physician (p = 0.02). Patients reporting greater levels of communication also had greater trust (r = 0.38; p &lt; 0.0001). Multivariate models evaluating the role of patient race, education, income, knowing which physician to talk to and how well the staff treated the patient found that being AA (aRR = 0.47; 95% CI: 0.21–0.88), having greater trust (aRR = 1.72; 95% CI:1.49–1.85) and better communication (aRR = 1.38; 95% CI: 1.03–1.65) were significantly associated with patient perception of excellent quality care (p &lt; 0.0001). Conclusions: Greater levels of physician communication about treatment and patient trust of their physician affect women's ratings of excellent cancer care quality. Efforts should be made to improve physician communication about treatment, particularly among AA women, to improve levels of trust and ratings of cancer care quality. No significant financial relationships to disclose.