tbuckley/cabot-search huggingface dataset:
Unraveling the Mysteries of Alpha<sub>1</sub>-Antitrypsin Deficiency
Authors: Allen B. Cohen
Journal: New England Journal of Medicine (1986)

alpha1-antitrypsin deficiency (also known as α1-protease-inhibitor deficiency) is a genetic disorder that has become known to physicians in most disciplines and to the lay public. Some of the genetic types (known as Pi types, including Z and S) cause sequestration of α1-antitrypsin in the liver, which leads to low concentrations of the substance in the blood. The great interest in this disease has been engendered by the prospect that pulmonary emphysema, its principal clinical manifestation, may soon be treated by replacing the protein lacking in the blood and lungs of patients. This issue of the Journal . . .
Establishment of a terminal prognosis prediction model by applying time series analysis to real-world data
Authors: Yu Uneno, Kei Taneishi, Masashi Kanai, Akiko Tamon, Kazuya Okamoto, Yoshitaka Nishikawa, J.B. Brown, Shigemi Matsumoto, Yasushi Okuno, Manabu Muto
Journal: Annals of Oncology (2015)
THU0088 Abnormal memory B-cell reconstitution following anti-CD20 therapy for autoimmune diseases predicts clinical relapse
Authors: G. Arumugakani, A. Rawstron, R. Tooze, A. Cherukuri, A. Varghese, E. Vital, P. Emery, D. McGonagle
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The advent of anti-CD20 therapy has significantly improved the management of various autoimmune conditions including rheumatoid arthritis (RA). The persistence of B-cells and/or plasmablasts in the immediate post-therapeutic phase (2 weeks) by highly sensitive flow cytometry has been shown to predict poor clinical response (1). However in patients with complete depletion, the return of clinical symptoms post B-cell reconstitution is variable, although clinical relapse is rare in the absence of return of B-lineage cells. <h3>Objectives</h3> To establish the reconstitution pattern of B-cells post anti-CD20 therapy in the phase prior to clinical relapse. <h3>Methods</h3> 79 samples from autoimmune patients and 36 disease controls were evaluated by 10-parameter flow cytometry. Scatter properties and surface expression of CD19, CD20, CD27 and CD38 was used to classify the B-lineage cells into transitional, naïve, memory B-cells and plasmablasts. Further analysis of 34 different surface markers on selected RA patients and controls was used to identify the 4 most informative markers that might help to predict disease relapse. <h3>Results</h3> We were able to classify the memory B-cells into 16 different subsets using the 4 markers identified as above. We identified a subset with plasmablast like phenotype (CD24<sup>Lo</sup> CD84<sup>Lo</sup> CD95<sup>Hi</sup> similar to plasmablasts and CD19, CD20 &amp; CD38 expression levels similar to memory B-cells), which constituted a higher proportion of memory B-cells and was the dominant subtype in the majority of RA patients relapsing post anti-CD20 therapy (14/18) compared to controls (2/10). The dominance of this subset was not seen in patients with Rituximab-naive activeRA (0/22) and only in 1 patient during remission (1/9) with different biologics/DMARDs. This abnormal reconstitution pattern was not seen in patients treated with Rituximab for B-cell lymphomas (0/4) or following pre-renal transplant Campath (Anti-CD52) conditioning (0/4). The samples from lymphoma patients in remission were collected 12-18 months since the last Rituximab dose and 3-6 months post-therapy in case of Campath. <h3>Conclusions</h3> The abnormal reconstitution of memory B-cell subsets is associated with clinical relapse following anti-CD20 therapy for RA and is likely to be related to the disease process rather than the direct effect of B-cell depletion. The patients with such altered memory B-cell reconstitution might benefit from early re-treatment. <h3>References</h3> Dass et al Arthritis Rheum. 2008 Oct;58(10):2993-9. <h3>Disclosure of Interest</h3> None Declared
Subcutaneous Compared with Intravenous Epoetin in Patients Receiving Hemodialysis
Authors: James S. Kaufman, Domenic J. Reda, Carol L. Fye, David S. Goldfarb, William G. Henderson, Jack G. Kleinman, Carlos A. Vaamonde
Journal: New England Journal of Medicine (1998)

Several studies have suggested that if recombinant human erythropoietin (epoetin) is administered subcutaneously rather than intravenously, a lower dose may be sufficient to maintain the hematocrit at a given level.
Myelodysplastic Syndrome is Often Associated with Solid Cancer, but Treatable: 21 Mds Cases at a Single Institution
Authors: Aya Ouchi, Masahiro Yokoyama, Kengo Takeuchi, Yoshiharu Kusano, Hideaki Nitta, Kyoko Ueda, Noriko Nishimura, Naoko Tsuyama, Yasuhito Terui, Kiyohiko Hatake
Journal: Annals of Oncology (2014)
Rodent Sensitization Is Associated With Worse Lung Function In Urban Adults With Asthma
Authors: M.C. Ong, P.N. Breysse, G.B. Diette, B.M. Thomas, P.J. Lenehan, J. Curtin-Brosnan, E.C. Matsui
Journal: Journal of Allergy and Clinical Immunology (2012)

Rodent sensitization and exposure is associated with asthma severity in urban children, but whether these are risk factors for asthma severity in adults with asthma is unclear. 63 non-smoking urban asthmatic adults (18-50y) underwent skin prick testing (SPT) to 14 common aeroallergens, including mouse and rat epithelia; pulmonary functioning testing; and completed questionnaires. Rodent sensitization was defined as a +SPT to either mouse or rat. A +SPT was defined as a ≥3mm net wheal. Outcomes were compared between rodent sensitized and non-rodent-sensitized subjects. Regression models were adjusted for gender, race, and number of +SPTs aside from mouse and rat. 38 (60%) were female, 49 (78%) were African American, and 21(33%) were rodent SPT+. 14(22%) were sensitized to rat, 13(20%) were sensitized to mouse and 8(13%) were sensitized to mouse and rat. Rodent sensitization was associated with low FEV1 (OR [95%CI]: 9.6 [2.0-45.2]), independent of race, gender, and number of +SPTs. Rodent sensitization was also associated with having been hospitalized for asthma, independent of race, gender, and number of +SPTs (OR [95%CI]: 3.6 [1.0-13.8]). Rodent sensitized and non-sensitized subjects had similar prevalences of symptoms in the past 2 weeks (OR [95%CI]: 1.6 [0.4-5.6]). Rat and mouse sensitization alone had similar relationships with these outcomes as being either rat or mouse sensitized. Rodent sensitization is associated with worse lung function in a community-based population of adults with asthma.
Tamoxifen in the Treatment of Breast Cancer
Authors: C. Kent Osborne
Journal: New England Journal of Medicine (1998)

Breast cancer is the most common cancer in women in the Western world. Because breast cancer is estrogen-dependent, reducing estrogen secretion by oophorectomy, hypophysectomy, or adrenalectomy can cause the cancer to regress. The need for these surgical procedures was reduced by the introduction of tamoxifen, which acts as an antiestrogen by inhibiting the binding of estrogen to estrogen receptors. Tamoxifen was approved by the Food and Drug Administration in 1977 for the treatment of women with advanced breast cancer and several years later for adjuvant treatment of primary breast cancer.1 Pharmacology and EndocrinologyPharmacologic and Pharmacokinetic PropertiesThe compound administered . . .
Abstract 5188: Phosphoinositide 3-kinase γ: Implications in breast cancer metastasis
Authors: Yan Xie, Joseph K. Kirui, Haihong Jiang, Caishu Deng, Yaping Tu
Journal: Cancer Research (2010)

Abstract Metastasis is the major cause of breast cancer mortality. Type I phosphatidylinositol 3-kinases (PI3Ks), including α, β, γ and δ, play a pivotal role in diverse cell processes such as proliferation and motility. Of these PI3Ks, PI3Kγ is especially intriguing because it is: 1) normally expressed primarily in white blood cells which have a physiological need to migrate and 2) is specifically activated by G-protein coupled receptors (GPCRs). We recently reported that aberrant Gi-coupled receptor signaling promotes breast cancer metastasis (Xie et al., Cancer Res. 69: 5743-5751). The goal of the present study was to determine roles of PI3Kγ in breast cancer metastasis. We first examined the levels of PI3Kγ in different breast cancer cell lines by RT-PCR and Western blot analysis. We then immunohistochemically analyzed PI3Kγ protein expression in histologically benign and neoplastic cells of archival human breast tissues. We also investigated effects of PI3Ks inhibitors on migration and invasion abilities of breast cancer cells in Transwell chamber assays. Finally, we determined effects of PI3Ks inhibitors on lamellipodia formation, a key step involved in cancer metastasis. Our data indicated that PI3Kγ mRNA and protein were not detected in a normal human breast epithelial cell line (MCF-10A) or non-metastatic breast cancer cells (MCF-7 and T47D), but was found in metastatic breast cancer MDA-MB-231 cells and MDA-MB-436 cells. In contrast, PI3Kα, β and δ are ubiquitously expressed in these cell lines. In addition, immunohistochemical staining using a PI3Kγ-specific antibody showed that the expression of PI3Kγ protein was significantly increased in invasive human breast carcinoma and in breast cancer metastases to a regional lymph node as compared to the adjacent benign breast tissues or the noninvasive ductal carcinoma in situ. Thus, PI3Kγ expression level correlates with the metastatic potential of breast cancer cells. Interestingly, migration and invasion of metastatic breast cancer cells were inhibited by a selective inhibitor of PI3Kγ but not α or β isoforms. Furthermore, blocking PI3Kγ but not α and β disrupted the Rac-dependent lamellipodia formation induced by the activation of Gi-coupled receptor CXC chemokine receptor 4, but not epidermal growth factor tyrosine kinase receptor. Taken together, these results indicate that up-regulated PI3Kγ conveys the metastatic signal initiated from GPCRs in breast cancer cells and suggest that PI3Kγ may be a novel therapeutic target for the treatment of breast cancers. Supported by Nebraska State LB692 (YX). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5188.
RESULTS OF PSYCHIATRIC TREATMENTS WITH A CONTROL SERIES
Authors: EARL D. BOND
Journal: American Journal of Psychiatry (1954)

1. This report on schizophrenia is a first step in building up a control group of the results of hospital psychiatric treatment. First shown are 393 consecutive schizophrenia patients admitted in 1925-34 before the coming of any shock treatments. 2. A comparison is made with 440 consecutive schizophrenic patients admitted in 1940-46 to the same hospital conditions but with insulin and electric shock series available and frequently used. 3. The shock treatments seem to be a push in the upward direction in schizophrenia: there are more recoveries sustained to the 5th year, more slightly improved, fewer unimproved, many more recovered and relapsed in the 5 years, and more recovered in the group that could not be followed. 4. Relapsed cases, both in and later than the 5th year period, raise the question as to whether shock treatments are enough. The fact must be taken into account that the 1940-46 patients had all the adjuvant hospital treatment that was given to the earlier control [see table 3 in source PDF] patients. Also the later patients had heard of and often seen the striking changes following shock treatments. One of the patients had been for 10 years in the hospital, the most obvious, regressed, typical schizophrenic: after a course of insulin he became a normal appearing, pleasantly talkative individual for a week and then he again regressed. The impact of the week's change on patients and nurses was powerful. 5. In the first table of results are included cases whose long duration before this hospitalization or treatment put a tremendous burden on therapy. In the control group 11 cases had run 6 to 7 years, 15 cases had run 8 to 10 years, 12 cases had run 11 to 15 years, and 10 cases had run 16 to 29 years. In the 1940-46 group 3 cases had run 6 or 7 years, 10 cases had run 11 to 15 years, and 7 cases had run 16 to 38 years. 6. The shorter the duration before therapy the better the results—with this truism goes the disturbing thought that the shorter the duration the more uncertain the diagnosis. 7. More patients recover and stay well under shock therapies but also more recover and relapse.
Q Fever Masquerading as Prostate Cancer Metastases
Authors: Michael J. Golden, Joanna R. Fair
Journal: Clinical Nuclear Medicine (2012)

We report a case of Q fever demonstrated on (99m)Tc methylene diphosphonate bone scan and fluorodeoxyglucose (FDG) PET/CT. A 66-year-old man with newly diagnosed, low-grade prostate cancer presented with abdominal and bone pain. Bone scan revealed multiple lesions suspicious for prostate cancer metastases. Because of liver abnormalities on noncontrast CT, an FDG PET/CT was performed and demonstrated FDG-avid sclerotic bone lesions, infiltrative liver disease, and retroperitoneal adenopathy. This appearance, thought unusual for low-grade prostate cancer, prompted extensive clinical evaluation for several months. Liver and iliac bone biopsies showed noncaseating granulomas without neoplasia. Extensive serologic evaluation eventually demonstrated elevated Q fever titers.
Abstract 3807: Integrative genomic profiling of pilocytic astrocytomas reveals location specific differential methylation and expression of brain developmental genes.
Authors: Sally R. Lambert, Hendrik Witt, Volker Hovestadt, Manuela Zucknick, Marcel Kool, Danita Pearson, Andrey Korshnov, Stefan Pfister, V. Peter Collins, David T. W. Jones
Journal: Cancer Research (2013)

Abstract Pilocytic astrocytomas (PA) are the most common brain tumor in pediatric patients and cause significant morbidity, particularly related to chronic neurological deficiencies. They are characterized by activating alterations in the mitogen activated protein kinase (MAPK) pathway, but little else is known about their development. To map the methylation profile of these tumors, we have performed a global DNA methylation analysis on 62 PAs and 7 normal cerebellum samples using Illumina 450K microarrays. Based on these data we have found two subgroups of PA that separate according to tumor location (infratentorial versus supratentorial), and have identified key neural developmental genes that are differentially methylated between the two groups, including NR2E1 and EN2. Integration with gene expression microarray data revealed significant expression differences that were typically associated with a strong positive correlation between methylation and expression. Differential methylation was most commonly identified within the gene body and/or 10 kb upstream/downstream of the gene body, and was, in part, accounted for by differences in the level of 5-hydroxymethylcytosine. We also identified a large number of differentially methylated genes between cerebellar PAs and normal cerebellum, which were again enriched for developmental genes. In addition, we found a significant association between differential methylation and SUZ12 binding sites, suggesting potential disruption of the polycomb repressor complex 2 (PRC2) in PA development. Taken together these data suggest the methylation profile of PA may reflect the cell of origin from which the tumors are derived, and highlights the potential disruption of key developmental regulators during tumorigenesis. These findings have implications for future clinical trials, as they suggest drug sensitivity and response may differ according to tumor location. Citation Format: Sally R. Lambert, Hendrik Witt, Volker Hovestadt, Manuela Zucknick, Marcel Kool, Danita Pearson, Andrey Korshnov, Stefan Pfister, V. Peter Collins, David T. W. Jones. Integrative genomic profiling of pilocytic astrocytomas reveals location specific differential methylation and expression of brain developmental genes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3807. doi:10.1158/1538-7445.AM2013-3807
Mediterranean Diet and Fracture Risk
Authors: Walter C. Willett
Journal: JAMA Internal Medicine (2016)

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AB1362 Validation of ICD-10 codes for stroke in patients with rheumatoid arthritis
Authors: M. Holmqvist, E. Gränsmark, L. Alfredsson, J. Askling
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> It is well known that patients with rheumatoid arthritis (RA) are at increased risk of ischemic heart disease. The results pertaining to risk of stroke in RA are conflicting; several studies have indicated no increased risk. When using administrative claims data to detect outcome, the validity of the registered codes are of pivotal importance. Misclassification of outcome could dilute risks that actually are present. In Sweden, hospitalization data are registered using international classification of diseases (ICD) codes. A validation study of stroke codes in the ICD-8 and ICD-9 based on the general population published in 1993 indicated that the codes for stroke in ICD-8 or ICD-9 classifications in the general unselected population had a high validity [1]; the positive predictive value of an ICD-8 or ICD-9 code indicating stroke was found to be 94% using medical charts and current clinical criteria to validate register information. There have been no studies of the validity of ICD-10 codes for stroke specifically among patients with RA. <h3>Objectives</h3> To assess the validity of the ICD-10 codes indicating ischemic and hemorrhagic stroke. <h3>Methods</h3> The Epidemiological Investigation of Rheumatoid Arthritis (EIRA) case-control study of incident RA was linked to the Swedish Hospital Discharge register and the charts of all individuals who after inclusion in EIRA were hospitalized with an ICD-10 code indicating IS (I63) or HS (I61) (n=36 events among 26 cases and 40 events among 30 controls) were reviewed. The gold standard was stroke verified via computed tomography (CT). In situations where the CT was normal but there was a clinically strong suspicion of stroke, the MONICA criteria [2]were used to classify IS. The positive predictive value (PPV) was calculated for both ICD-codes, overall, and stratified by RA-status. <h3>Results</h3> Out of the 68 listings with I63 (IS), 62 were verified as IS either via CT or the MONICA criteria. Out of the 7 listings with I61 (HS), 7 were verified as HS via CT. The PPV for IS given a listing of I63 was 91% and for HS given a listing of I61 was 100%. Overall, the PPV of IS and HS combined was 92% among RA patients and 90% among the controls. <h3>Conclusions</h3> The validity of ICD-10 listings of stroke in the Swedish Hospital Discharge register is high, and can safely be used in register linkage studies. This also applies for patients with RA. <h3>References</h3> Lindblad, U., et al., Validity of register data on acute myocardial infarction and acute stroke: the Skaraborg Hypertension Project. Scand J Soc Med, 1993; 21(1): p. 3-9. WHO, MONICA manual, Part IV: Event registration, Section 2: Stroke event registration data component. 1990, World Health Organization: Geneva. <h3>Disclosure of Interest</h3> None Declared
Results of a Randomized Trial of Partner Notification in Cases of HIV Infection in North Carolina
Authors: Suzanne E. Landis, Victor J. Schoenbach, David J. Weber, Manjoo Mittal, Baldev Krishan, Karen Lewis, Gary G. Koch
Journal: New England Journal of Medicine (1992)

We sought to compare two methods of notifying sex partners of subjects infected with the human immunodeficiency virus (HIV) or persons who had shared needles with them (needle-sharing partners): "patient referral," in which the responsibility for notifying partners was left to the patient, and "provider referral," in which providers attempted to notify partners.
SINGLE CELL DERIVED CLONAL ANALYSIS OF HUMAN GLIOBLASTOMA LINKS FUNCTIONAL AND GENOMIC HETEROGENEITY
Authors: P. B. Dirks, M. Meyer, J. Reimand, X. Lan, R. Head, X. Zhu, M. Kushida, J. Bayani, J. C. Pressey, A. Lionel, I. D. Clarke, M. Cusimano, J. Squire, S. Scherer, M. Bernstein, M. A. Woodin, G. D. Bader
Journal: Neuro-Oncology (2014)

BACKGROUND: Glioblastoma (GBM) is a cancer comprised of morphologically, genetically and phenotypically diverse cells. However, an understanding of the functional significance of intratumoral heterogeneity is lacking. METHODS: We devised a method to isolate and functionally profile tumorigenic clones from patient glioblastoma samples. RESULTS: Individual clones demonstrated unique proliferation and differentiation abilities. Importantly, naïve patient tumors included clones that were temozolomide (TMZ) resistant, indicating that resistance to conventional GBM therapy preexists in untreated tumors at a clonal level. Further, candidate therapies for resistant clones were identified with clone-specific drug screening. Genomic analyses identified genes and pathways that associate with specific functional behavior of single clones. In particular, increased expression and signaling of the autocrine/paracrine γ-aminobutyric acid (GABA) receptor GABRA3 correlates with TMZ sensitivity and patient outcome. CONCLUSIONS: Our results suggest that functional clonal profiling used to identify tumorigenic and drug resistant tumor clones will lead to the discovery of new GBM clone-specific treatment strategies. SECONDARY CATEGORY: n/a.
Pheochromocytoma as an Inherited Abnormality
Authors: Charles T. Carman, Richard E. Brashear
Journal: New England Journal of Medicine (1960)

ALTHOUGH the first pathological description of pheochromocytoma, by Fränkel,1 appeared in 1886, it was not until 1922 that the association of pheochromocytoma and paroxysmal hypertension was described by Labbé et al.2 A cause- and-effect relation was established by Mayo3 in 1927, when he demonstrated that removal of such a tumor resulted in complete relief of the associated hypertension. Mayo's report stimulated widespread medical interest in pheochromocytoma as a potentially curable cause of hypertension. Although numerous publications have emphasized the diagnostic and therapeutic aspects of this condition, the familial occurrence of pheochromocytoma has received relatively little attention.The purpose of this . . .