tbuckley/cabot-search huggingface dataset:
A food-borne outbreak of hepatitis A virus (HAV) infection in a secondary school in Upper Normandy, France, in November 2006
Authors: N G Schwarz, M Revillion, A M Roque-Afonso, E Dussaix, M Giraud, C Liberpre, E Couturier, E Delarocque Astagneau
Journal: Eurosurveillance (2008)

In November 2006, six symptomatic cases of hepatitis A in pupils of a secondary school in Upper Normandy, France, were reported to the district health service. This paper describes the outbreak investigation undertaken with the aim to identify the vehicle and source of infection, implement control measures and estimate the size of the outbreak. A primary case at the secondary school was defined as a pupil or a member of the staff with IgM anti-HAV detected in the serum and with onset of symptoms between 12 and 21 November 2006; a secondary case was defined as a contact to a primary case and who developed symptoms and had IgM anti-HAV two to seven weeks later. We performed a case control study of primary cases, controls being pupils visiting the same school (cases/controls 1:4) and inspected the canteen facilities. All 13 canteen employees were examined for anti-HAV IgM antibodies. A phylogenetic analysis of HAV of cases was performed. We identified 10 primary and 5 secondary cases. Among primary cases 90% reported eating liver pate at the canteen compared to 62% among controls (OR 5.5, 95% CI 0.62-256.9). One liver pate sample contained markers of faecal contamination. HAV genotypes were of one identical type. All 13 canteen employees were negative for IgM anti-HAV while four had anti-HAV total antibodies. We found deficiencies regarding food preparing procedures and insufficient hand washing facilities. The vehicle of the outbreak was believed to be the liver pate but the source of HAV could not be identified. Insufficient facilities in the canteen hindered staff from maintaining a high hygiene standard and were subsequently improved.
Outcome Indicators in Primary Sclerosing Cholangitis: Interim Analysis Of The Value-Based Medicine In Hepatology (VBMH) Study
Authors: L Fabris, A Ciaccio, S Okolicsanyi, M Rota, P Cortesi, L Belli, S Fagiuoli, L Scalone, G Cesana, L Mantovani, M Strazzabosco
Journal: Hepatology (2015)
HTLV-1 Viral Factor HBZ Induces CCR4 to Promote T-cell Migration and Proliferation
Authors: Kenji Sugata, Jun-ichirou Yasunaga, Haruka Kinosada, Yuichi Mitobe, Rie Furuta, Mohamed Mahgoub, Chiho Onishi, Kazutaka Nakashima, Koichi Ohshima, Masao Matsuoka
Journal: Cancer Research (2016)

Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia-lymphoma (ATL) and other inflammatory diseases in infected individuals. However, a complete understanding of how HTLV-1 transforms T cells is lacking. Expression of the chemokine receptor CCR4 on ATL cells and HTLV-1-infected cells suggested the hypothesis that CCR4 may mediate features of ATL and inflammatory diseases caused by HTLV-1. In this study, we show that the constitutively expressed HTLV-1 bZIP factor (HBZ) encoded by HTLV-1 is responsible for inducing CCR4 and its ability to promote T-cell proliferation and migration. Ectopic expression of HBZ was sufficient to stimulate expression of CCR4 in human and mouse T cells. Conversely, HBZ silencing in ATL cell lines was sufficient to inhibit CCR4 expression. Mechanistic investigations showed that HBZ induced GATA3 expression in CD4(+) T cells, thereby activating transcription from the CCR4 promoter. In an established air pouch model of ATL, we observed that CD4(+) T cells of HBZ transgenic mice (HBZ-Tg mice) migrated preferentially to the pouch, as compared with those in nontransgenic mice. Migration of CD4(+) T cells in HBZ-Tg mice was inhibited by treatment with a CCR4 antagonist. Proliferating (Ki67(+)) CD4(+) T cells were found to express high levels of CCR4 and CD103. Further, CD4(+) T-cell proliferation in HBZ-Tg mice was enhanced by coordinate treatment with the CCR4 ligands CCL17 and 22 and with the CD103 ligand E-cadherin. Consistent with this finding, we found that ATL cells in clinical skin lesions were frequently positive for CCR4, CD103, and Ki67. Taken together, our results show how HBZ activates CCR4 expression on T cells to augment their migration and proliferation, two phenomena linked to HTLV-1 pathogenesis. Cancer Res; 76(17); 5068-79. ©2016 AACR.
Abstract 2075: Replication of Association of Newly Identified Loci With Metabolic and Lipid-related Traits in Asian Indian Sikhs
Authors: Dharambir K Sanghera, Latonya Been, Akhil Singhal, Lyda Ortega, Sarju Ralhan, Narinder K Mehra
Journal: Circulation (2009)

Recent genome-wide association scans (GWAS) have implicated several loci with metabolic and lipid related traits. This investigation seeks to examine the role of six GWAS-derived loci ( CETP  rs3764241;  APOA5-A4-C3-A1  rs12286037;  APOE-C1-C4  rs4420638;  CELSR2-PSRC1-SORT1 rs599839,  CDKN2A-CDKN2B  rs1333049; and  PON1  rs662) with type 2 diabetes (T2D) and quantitative serum lipids using a case-control cohort from our Sikh Diabetes Study (SDS). We genotyped these SNPs on 2,194 subjects including 1,379 T2D cases and 815 controls. Three of the six loci revealed significant association with T2D;  CELSR2-PSRC1-SORT1  (rs599839) [OR 1.55; p=0.018],  CDKN2A-CDKN2B  (rs1333049) [OR 1.18; p=0.013], and  PON1 ( rs662) [OR 1.24; p=0.021] in an additive model after adjusting for age, gender and body mass index (BMI). We also examined the impact of these variants on quantitative metabolic traits (fasting blood glucose (FBG) and serum lipids) including age, gender, medication and disease status as covariates in the model. The variant near  CELSR2-PSRC1-SORT1  (rs599839) was associated with increased FBG levels in controls ( β =0.059; p=0.009). The strongest association with HDL cholesterol was observed at rs3764241 in the  CETP  gene ( β =0.072; p=0.002), where HDL levels were increased by 3.51 mg/dl in two ‘A’ allele carriers vs. no ‘A’ carriers. The ‘A’ allele carriers also revealed a significant decrease in triglycerides ( β =−0.063; p=0.013) and VLDL cholesterol ( β =−0.08; p=0.009). Our data also replicated the association of ‘T’ allele of  APOA5-A4-C3-A1  rs12286037 with increased triglyceride levels ( β =0.089; p=0.001). However, we could not confirm the association of  APOE-C1-C4  (rs4420638) variant with any lipid or T2D-related trait. The replication of positive association of most of these loci in an independently ascertained sample from South Asia strongly confirm the underlying role of these genes in the pathophysiology of hyperlipidemia, T2D and cardiovascular disease. As the overall contribution of these loci for affecting serum lipids in this study was ≤ 3%, perhaps the causal SNPs in these genes with larger effects still need to be identified. Further dense genotyping and deep sequencing may help identifying putative functional loci of therapeutic importance.
A Large Cohort Analysis of CMV Viral Load and Ganciclovir-Related Neutropenia in Nonmyeloablative (NM-HCT) and Myeloablative (M-HCT) Allogeneic Hematopoietic Cell Transplant Recipients.
Authors: Hirohisa Nakamae, Katharine A. Kirby, Brenda M. Sandmaier, Lalita Norasetthada, David Maloney, Michael Maris, Chris Davis, Lawrence Corey, Rainer Storb, Michael Boeckh
Journal: Blood (2007)
Statin Use Protects Against Systemic Inflammation in a Geriatric Population: The Brazilian Study on Healthy Aging
Authors: Sameer Shaharyar, Omar Jamal, Ehimen C. Aneni, Wladimir M. Freitas, Luiz A. Quaglia, Rafaela C. de Paula, Raul D. Santos, Michael J. Blaha, Seth S. Martin, Roger S. Blumenthal, Arthur S. Agatston, Andrei C. Sposito, Khurram Nasir
Journal: Circulation (2013)
Abstract 2549: Tyrosyl-DNA phosphodiesterase 1 (TDP1) is critical for the repair of DNA breaks induced by sapacitabine, a nucleoside antimetabolite in clinical trials targeted to ATM- and BRCA-deficient tumors
Authors: Muthana Al Abo, Xiaojun Liu, William Plunkett, Yves Pommier
Journal: Cancer Research (2015)

Abstract 2′-C-cyano-2′-deoxy-1-β-D-arabino-pentofuranosylcytosine (CNDAC) is a nucleoside analogue and the active metabolite of the anticancer drug, sapacitabine. The cytotoxic activity of CNDAC is achieved by incorporation of its nucleoside triphosphate metabolite into genomic DNA during replication, which subsequently undergoes beta-elimination that generates a single-strand break with 3′-end blocking DNA lesion. Subsequent DNA replication converts the nick into a double strand break. Earlier investigations demonstrated that cells lacking homologous recombination function are sensitized 20- to 100-fold to CNDAC. Because tyrosyl-DNA phosphodiesterase 1 (TDP1) efficiently hydrolyzes 3′-blocking ends, we tested its role in the repair of CNDAC-induced DNA lesions and the potential cellular tolerance to CNDAC. Here we show that cells lacking TDP1 (TDP1-/- DT40 cells) exhibited marked hypersensitivity to CNDAC indicating the importance of TDP1 for the repair of CNDAC-induced DNA damage. Although the 3′-end blocking DNA lesions caused by another arabinosyl-nucleoside analog, cytosine arabinoside (cytarabine, AraC) and the topoisomerase I inhibitor camptothecin (CPT) are also repaired by TDP1, inactivation of homologous recombination, including BRCA1 and BRCA2, rendered cells hypersensitive to CNDAC and CPT but not to AraC. On the other hand, cells lacking PARP1/2 were hypersensitive to CPT only. Consistent with earlier findings, DT40 cells deficient in BRCA1, BRCA2, FANCD2, and ATM were sensitized to CNDAC. Thus, the present study has identified TDP1 as an additional mechanism that contributes to the repair of CNDAC-induced DNA lesions. It also demonstrates the differential involvement of DNA repair pathways that underlie the resistance to CNDAC, AraC and camptothecins, and provides a rationale for using sapacitabine to treat various types of cancers with preexisting defects in DNA repair pathways. Citation Format: Muthana Al Abo, Xiaojun Liu, William Plunkett, Yves Pommier. Tyrosyl-DNA phosphodiesterase 1 (TDP1) is critical for the repair of DNA breaks induced by sapacitabine, a nucleoside antimetabolite in clinical trials targeted to ATM- and BRCA-deficient tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2549. doi:10.1158/1538-7445.AM2015-2549
Long Term Follow-Up Of De Novo Or Minimally Treated Burkitt Lymphoma/Leukemia (BL/B-ALL) After Frontline Therapy Per The Hyper-CVAD Regimen With Or Without Rituximab: 20-Year Cumulative Experience
Authors: Preetesh Jain, Hagop M Kantarjian, Jorge E. Cortes, Elias J. Jabbour, Stefan H. Faderl, William G. Wierda, Guillermo Garcia-Manero, Alessandra Ferrajoli, Srdan Verstovsek, Jan A. Burger, Luis Fayad, Jorge Romaguera, Rebecca Garris, Farhad Ravandi, Susan O'Brien, Deborah Thomas
Journal: Blood (2013)
Phase I clinical trial of galeterone (TOK-001), a multifunctional antiandrogen and CYP17 inhibitor in castration resistant prostate cancer (CRPC).
Authors: Robert B. Montgomery, Mario A. Eisenberger, Matthew Rettig, Franklin Chu, Roberto Pili, Joe Stephenson, Nicholas J. Vogelzang, Jodie Morrison, Mary-Ellen Taplin
Journal: Journal of Clinical Oncology (2012)

4665 Background: Galeterone is an oral steroid analog that suppresses prostate cancer growth by inhibiting CYP17, blocking androgen receptor and reducing androgen receptor levels. Methods: Open label, multicenter dose-finding study assessing the safety, pharmacokinetics and clinical effect of escalating doses of galeterone in chemotherapy naïve CRPC patients (pts). Pts were enrolled in cohorts from 650-2,600mg of galeterone daily for 12 wks. Study also explored effects of food supplement and scheduling. Pts remained on study until disease progression or dose limiting toxicity. Results: Pt characteristics included median age 69 (47-92), median PSA 24 (6-200), and 46.9% with metastases. 36 of 49 pts completed 12 wks of study with early discontinuation for toxicity (6), progression (5), or withdrawal of consent (2). Maximal tolerated dose was not reached. The frequency of AEs was 58% grade 1, 30% grade 2, 8% grade 3 and 1% grade 4. Transient LFT elevations were seen in 15 men (5 with suspected or confirmed Gilberts). There was no trend for increasing toxicity with dose escalation and no PK difference in Gilberts pts. 9 SAEs were reported with one considered related to galeterone (rhabdomyolysis with acute renal failure in the context of high dose statin use). Overall 11/49 pts (22%) demonstrated &gt;50% PSA decline and an additional 13/49 (26%) had 30-50% declines. Partial response by RECIST was seen in 2 pts. Consistent with lyase inhibition, increased corticosteroids and suppressed androgens were seen with dose escalation. Analysis of limited plasma collected 4 - 30 hours after dosing showed high interpatient variability with no consistent relationship to dose or time after dosing. Conclusions: Galeterone was well tolerated in CRPC pts and demonstrated clinical activity. Galeterone is being reformulated with additional PK and phase II trials planned. [Table: see text]
Lack of Independent Association Between Fatty Pancreas and Incidence of Type 2 Diabetes: 5-Year Japanese Cohort Study
Authors: Hajime Yamazaki, Toru Tsuboya, Akio Katanuma, Yoshihisa Kodama, Shinichi Tauchi, Mitsuru Dohke, Hiroyuki Maguchi
Journal: Diabetes Care (2016)

Previous cross-sectional studies have shown that attenuation in the pancreas seen on unenhanced computed tomography (CT) scans was inversely correlated with histologic pancreatic fat, and that fatty pancreas was associated with type 2 diabetes mellitus (T2DM). However, no longitudinal study has evaluated whether fatty pancreas increases the incidence of T2DM. We conducted a cohort study to investigate the association between fatty pancreas and the incidence of T2DM.A total of 813 participants without diabetes underwent health checks by unenhanced CT scanning in 2008 and 2009, and were observed for a median follow-up period of 5.06 (interquartile range 3.01-5.92) years. Attenuation in three regions of the pancreas seen on an unenhanced CT scan was measured, and the mean pancreatic attenuation was calculated to evaluate fatty pancreas at baseline; the more severe the fatty pancreas, the lower the mean pancreatic attenuation. The incident T2DM hazard ratios (HRs) for the association between fatty pancreas and T2DM incidence were estimated by Cox proportional hazards models adjusted for age, sex, BMI, liver attenuation seen on unenhanced CT scan, and alcohol intake of ≥20 g/day.T2DM occurred in 62 participants (7.6%) during the follow-up period. The higher pancreas attenuation (i.e., less pancreatic fat) at baseline was associated with decreased T2DM incidence in a univariate analysis (crude HR 0.97 [95% CI 0.96-0.99]); and fatty pancreas (lower pancreas attenuation) was positively associated with increased T2DM incidence. However, the association was substantially explained by the confounders (multivariate HR 1.00 [95% CI 0.98-1.02]).Fatty pancreas was not independently associated with future T2DM.
Differential diagnosis and classification of apathy
Authors: R S Marin
Journal: American Journal of Psychiatry (1990)

This paper discusses the definition of apathy, reviews its differential diagnosis, and proposes a classification for the conditions that may produce it. Apathy is defined as diminished motivation not attributable to diminished level of consciousness, cognitive impairment, or emotional distress. In its differential diagnosis, abulia, akinesia and akinetic mutism, depression, dementia, delirium, despair, and demoralization must be ruled out. Classification of apathy is organized in terms of its adaptive and functional consequences, its relationship to personality or to sociocultural or environmental events, and its association with psychiatric, neurological, and medical disorders. An approach to assessment and treatment is proposed.
William Tipping Leads American cancer Society Into 1990's
Authors: W M Tipping
Journal: JNCI Journal of the National Cancer Institute (1989)

William Tipping Leads American cancer Society Into 1990's Get access JNCI: Journal of the National Cancer Institute, Volume 81, Issue 5, 1 March 1989, Pages 327–330, https://doi.org/10.1093/jnci/81.5.327 Published: 01 March 1989
Audit in Mid-Glamorgan also shows major problems with management of hypertension
Authors: A. J Burr
Journal: BMJ (1996)

EDITOR,—T P Fahey and T J Peters's paper highlights the fact that blood pressure guidelines vary considerably in the way they determine control of hypertension.1 Colleagues and I are currently carrying out an audit of hypertensive patients, and I report here some preliminary data on our findings from this audit in Upper Rhondda Fawr, Mid-Glamorgan.

The audit involves five local practices and 10 community pharmacists, who regularly assess control of blood pressure and other, related variables in …
Interleukin-13 Activates Distinct Cellular Pathways Leading to Ductular Reaction, Steatosis, and Fibrosis
Authors: Richard L. Gieseck, Thirumalai R. Ramalingam, Kevin M. Hart, Kevin M. Vannella, David A. Cantu, Wei-Yu Lu, Sofía Ferreira-González, Stuart J. Forbes, Ludovic Vallier, Thomas A. Wynn
Journal: Immunity (2016)

Fibroproliferative diseases are driven by dysregulated tissue repair responses and are a major cause of morbidity and mortality because they affect nearly every organ system. Type 2 cytokine responses are critically involved in tissue repair; however, the mechanisms that regulate beneficial regeneration versus pathological fibrosis are not well understood. Here, we have shown that the type 2 effector cytokine interleukin-13 simultaneously, yet independently, directed hepatic fibrosis and the compensatory proliferation of hepatocytes and biliary cells in progressive models of liver disease induced by interleukin-13 overexpression or after infection with Schistosoma mansoni. Using transgenic mice with interleukin-13 signaling genetically disrupted in hepatocytes, cholangiocytes, or resident tissue fibroblasts, we have revealed direct and distinct roles for interleukin-13 in fibrosis, steatosis, cholestasis, and ductular reaction. Together, these studies show that these mechanisms are simultaneously controlled but distinctly regulated by interleukin-13 signaling. Thus, it may be possible to promote interleukin-13-dependent hepatobiliary expansion without generating pathological fibrosis.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJjNTRlNWI0MjExZWM3ZmY3MTRjNTBlZmExYmJhMmM2OCIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc4MzY2OTgwfQ.hREtsfZSpPN_jm_nlxQ8TJ1UyaLqkVI6Xc5WebL2-Iq33VX9say-45ADNlMjyM5weBXLHS9isrtvtCTOs7cd6iq2MNilwCZaEWdPK3C9kaxN_r63rR7XHlEfNeu-xAlo0YiIjqNT3GwGIlt4TIcUrseH0SXuNmRSGyueeDoGY53GZs5rVQyx9rPVwLyq2plJvSO7BIpyj24A5mFslFYflWP105QsY9ckJ42w7aT3XOly8XoeEeg66EPMQqk-hmu2J_gbzIIx_r6LX64gP6k89oy86YrxFCKPuF0qS4CIHUkP0C4tOo3ck57fb2yn0l07keAJWcDURrB_m2nXIbXANQ(mp4, (20.16 MB) Download video
Estrogens Act As a Dorsal-Ventral Limiting Factor To Pattern The Hematopoietic Stem Cell Niche
Authors: Kelli J. Carroll, Michael C Dovey, Maija K Garnaas, Claire C Cutting, Gregory M Frechette, Virginie Esain, Sahar Nissim, Wanda Kwan, James M Harris, Daniel Gorelick, Marnie Halpern, Wolfram Goessling, Trista E. North
Journal: Blood (2013)
HD Flow Cytometry: An Improved Way to Quantify Cellular Interactions with Nanoparticles
Authors: Laura I. Selby, Nachnicha Kongkatigumjorn, Georgina K. Such, Angus P. R. Johnston
Journal: Advanced Healthcare Materials (2016)

Histogram deconvolution flow cytometry enables improved quantification of nanomaterial-cell interactions. The algorithm identifies the positive cells in highly overlapped populations and calculates the fluorescence intensity of the positive population. This technique performs better than commercially available methods with the additional benefit of visualizing the output.
Case 20-1977
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Allan I. Sandler, John C. Long
Journal: New England Journal of Medicine (1977)

Presentation of CaseA 71-year-old man was admitted to the hospital because of back pain.He was well until one month previously, when he began to complain of lumbar pain that radiated to both flanks and was aggravated by motion. Two weeks later he became increasingly constipated, with occasional abdominal cramps. A physician found a mass, 4 by 6 cm, in the right upper abdominal quadrant; the mass was nontender, moved slightly with respiration and was separate from the liver. Sigmoidoscopic examination to 24 cm revealed no abnormality. An automated scan of a blood specimen disclosed anemia and a slight . . .
A phase Ib study of gemcitabine plus PEGPH20 (pegylated recombinant human hyaluronidase) in patients with stage IV previously untreated pancreatic cancer.
Authors: Sunil R. Hingorani, William Proctor Harris, J. Thaddeus Beck, Boris A. Berdov, Stephanie Ann Wagner, Eduard M. Pshevlotsky, Sergei Tjulandin, Oleg Gladkov, Randall F. Holcombe, Ping Jiang, Daniel C. Maneval, Joy Zhu, Craig E. Devoe
Journal: Journal of Clinical Oncology (2013)

4010 Background: PEGPH20 is a PEGylated version of human recombinant hyaluronidase. In preclinical studies, PEGPH20 depleted pancreatic cancers of their high hyaluronan (HA) content. In a genetically-engineered murine model of PDA, PEGPH20 + gemcitabine (Gem) significantly prolonged survival compared to Gem alone. In Ph1 PEGPH20 monotherapy studies, the MTD was 3.0 μg/kg. The most common AEs were musculoskeletal events (MSEs). Methods: This was a dose-escalation study to find the recommended Phase 2 dose (RP2D) of PEGPH20 in combination with Gem in patients (pts) with Stage IV previously untreated pancreatic cancer. Pts received PEGPH20 at 1, 1.6, or 3 μg/kg IV twice a week for Wks 1-4, weekly for Wks 5-7, then 1 wk rest. Dose escalation was based on safety. Gem was given at 1000 mg/m 2 IV once a week for Wks 1-7, then 1 wk rest. Thereafter, PEGPH20 + Gem were given once a week for 3 wks in 4-wk cycles. Dexamethasone was given pre and post PEGPH20 doses. Results: Of the 28 pts enrolled, the majority had a Karnofsky performance status of 80%, and 85%/19%/26% of pts had liver/lung/visceral metastases. The median age was 58 yrs. Four pts received PEGPH20 at 1 μg/kg, 4 at 1.6 μg/kg, and 20 at 3 μg/kg. The RP2D was 3 μg/kg. Treatment duration ranged from 1-274 days; 5 pts remain on study. Treatment was generally well tolerated. Ten pts had 1 Gem dose reduction, 2 pts had 1 PEGPH20 dose reduction (3 to 1.6 µg/kg), but no pt had a DLT. The most common PEGPH20-related AEs were MSEs (25% Gr1; 18% Gr2) and fatigue (21% Gr1; 11% Gr2). Objective response was assessed by an independent central radiologist using RECIST 1.1. Of the 21 pts evaluable for efficacy, 7 had partial response (PR) for an overall response rate (ORR) of 33%, and 9 had stable disease for ≥ 2 mo. Tumor biopsies from 12 pts were evaluable for HA staining. HA was high in 9 and low in 3. Of the 9 with high HA staining, 5 had PR (56% ORR); HA data were not available for the other 2 PR pts. PK results show dose-dependent exposure consistent with data from PEGPH20 monotherapy studies. Conclusions: PEGPH20 in combination with Gem is generally well tolerated in advanced pancreatic cancer and shows promising efficacy, especially in pts with high intratumoral HA content. Clinical trial information: NCT01453153.