tbuckley/cabot-search huggingface dataset:
Dissection of the Major Hematopoietic Quantitative Trait Locus in Chromosome 6q23.3 Identifies miR-3662 as a Player in Hematopoiesis and Acute Myeloid Leukemia
Authors: Sophia E. Maharry, Christopher J. Walker, Sandya Liyanarachchi, Sujay Mehta, Mitra Patel, Maryam A. Bainazar, Xiaomeng Huang, Malori A. Lankenau, Kevin W. Hoag, Parvathi Ranganathan, Ramiro Garzon, James S. Blachly, Denis C. Guttridge, Clara D. Bloomfield, Albert de la Chapelle, Ann-Kathrin Eisfeld
Journal: Cancer Discovery (2016)

Chromosomal aberrations and multiple genome-wide association studies (GWAS) have established a major hematopoietic quantitative trait locus in chromosome 6q23.3. The locus comprises an active enhancer region, in which some of the associated SNPs alter transcription factor binding. We now identify miR-3662 as a new functional driver contributing to the associated phenotypes. The GWAS SNPs are strongly associated with higher miR-3662 expression. Genome editing of rs66650371, a three-base-pair deletion, suggests a functional link between the SNP genotype and the abundance of miR-3662. Increasing miR-3662's abundance increases colony formation in hematopoietic progenitor cells, particularly the erythroid lineage. In contrast, miR-3662 is not expressed in acute myeloid leukemia cells, and its overexpression has potent antileukemic effects in vitro and in vivo Mechanistically, miR-3662 directly targets NF-κB-mediated transcription. Thus, miR-3662 is a new player of the hematopoietic 6q23.3 locus.The characterization of miR-3662 has identified a new actor in the prominent hematopoietic quantitative trait locus in chromosome 6q23.3. The mechanistic insights into miR-3662's function may reveal novel or only partially known pathways for normal and malignant hematopoietic cell proliferation. Cancer Discov; 6(9); 1036-51. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.
Progression-free and overall survival in ovarian cancer patients treated with CVac, a mucin 1 dendritic cell therapy in a randomized phase 2 trial
Authors: H. J. Gray, B. Benigno, J. Berek, J. Chang, J. Mason, L. Mileshkin, P. Mitchell, M. Moradi, F. O. Recio, C. M. Michener, A. Alvarez Secord, N E. Tchabo, J. K. Chan, J. Young, H. Kohrt, S. E. Gargosky, J. C. Goh
Journal: Journal for ImmunoTherapy of Cancer (2016)

CAN-003 was a randomized, open-label, Phase 2 trial evaluating the safety, efficacy and immune outcomes of CVac, a mucin 1 targeted-dendritic cell (DC) treatment as a maintenance therapy to patients with epithelial ovarian cancer (EOC).Patients (n = 56) in first (CR1) or second clinical remission (CR2) were randomized (1:1) to standard of care (SOC) observation or CVac maintenance treatment. Ten doses were administered over 56 weeks. Both groups were followed for progression-free survival (PFS) and overall survival (OS).Fifty-six patients were randomized: 27 to SOC and 29 to CVac. Therapy was safe with only seven patients with Grade 3-4 treatment-emergent adverse events. A variable but measurable mucin 1 T cell-specific response was induced in all CVac-treated and some standard of care (SOC) patients. Progression free survival (PFS) was not significantly longer in the treated group compared to SOC group (13 vs. 9 months, p = 0.36, hazard ratio [HR] = 0.73). Analysis by remission status showed in the CR1 subgroup a median PFS of 18 months (SOC) vs. 13 months (CVac); p = 0.69 (HR = 1.18; CI 0.52-2.71). However CR2 patients showed a longer median PFS in the CVac-treated group (median PFS not yet reached, >13 vs. 5 months; p = 0.04, HR = 0.32 CI). OS for CR2 patients at 42 months of follow-up showed a difference of 26 months for SOC vs. > 42 months for CVac-treated (as median OS had not been reached; HR = 0.17 (CI 0.02-1.4) with a p = 0.07).CVac, a mucin 1-dendritic cell maintenance treatment was safe and well tolerated in ovarian cancer patients. A variable but observed CVac-derived, mucin 1-specific T cell response was measured. Notably, CR2 patients showed an improved PFS and lengthened OS. Further studies in CR2 ovarian cancer patients are warranted (NCT01068509).NCT01068509. Study Initiation Date (first patient screened): 20 July 2010. Study Completion Date (last patient observation): 20 August 2013, the last patient observation for progression-free survival; 29 April 2015, the last patient was documented regarding overall survival.
Trends in Stimulant Medication Use in Commercially Insured Youths and Adults, 2010-2014
Authors: Mehmet Burcu, Julie M. Zito, Leanne Metcalfe, Howard Underwood, Daniel J. Safer
Journal: JAMA Psychiatry (2016)

Stimulants are the most commonly prescribed treatment of attention-deficit/hyperactivity disorder (ADHD) in youths, and according to a nationally representative US household survey, there has been a sizeable increase in stimulant use among youth, from 4.0% between 1996 and 1998 to 6.6% between 2010 and 2012. 1 Also, during the last decade, the US Food and Drug Administration approved an indication for stimulant use in adults to treat ADHD.Studies of office-based physician visits by adults showed that the proportion of visits with a prescribed stimulant grew 7-fold, from 0.1% between 1994 and 1997 to 0.7% between 2006 and 2009, 2 and the percentage of visits with ADHD diagnosis doubled from 0.3% between 1999 and 2002 to 0.7% between 2007 and 2010. 3 Also, compared with youth ADHD visits, adult ADHD visits comprised a distinctly larger proportion of female and commercially insured visits. 3However, little is known about the trends in stimulant use within the past few years, specifically within commercially insured US populations.This study uses data from a large, commercially insured population to characterize recent trends and patterns of stimulant use according to age and sex.
Corrigendum to “The incidence, age at diagnosis of breast cancer in Iraqi Kurdish population and comparison to some other countries in Middle-East and West” [Int. J. Surg. 13 (2015) 71–75]
Authors: Sherko Abdullah Molah Karim, Hawar Hasan Ali Ghalib, Sangar Abdullah Mohammed, Fattah Hama Rahim Fataah
Journal: International Journal of Surgery (2016)
Case 12-1983
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Zareh N. Demirjian, Nancy L. Harris
Journal: New England Journal of Medicine (1983)

Presentation of CaseA 78-year-old woman was admitted to the hospital because of fever of unknown origin.There was a long history of hypertension, treated with methyldopa. She was otherwise well until three months before admission, when she began to have episodes of fever, accompanied by a loss of 14 kg in weight. Seven weeks before entry she was admitted to another hospital, where evaluation revealed anemia. The bilirubin and alkaline phosphatase were elevated. A computed tomographic (CT) scan of the liver (Fig. 1) showed multiple hepatic cysts. Microscopical examination of an aspirated biopsy specimen of the liver was interpreted . . .
Temperament and hypercortisolemia in depression
Authors: P R Joyce, R T Mulder, C R Cloninger
Journal: American Journal of Psychiatry (1994)

The authors examined the relationships among depression severity, melancholia, and cortisol level and the relationship between temperament, as measured with the Tridimensional Personality Questionnaire, and cortisol level.Morning and afternoon cortisol levels of 40 healthy comparison subjects and 96 patients with major depression were measured. The depressed patients were rated for depression severity and melancholia, and they completed the Tridimensional Personality Questionnaire.Temperament, especially dependence and extravagance, but not depressive symptoms, was the major determinant of the hypercortisolemia observed in the depressed patients.For research in biological psychiatry to advance, more attention needs to be paid to the individual differences in biology that underlie any state-dependent biologic dysfunction.
Effects of legal pressure on prognosis for treatment of drug dependence
Authors: R J Harford, J C Ungerer, J K Kinsella
Journal: American Journal of Psychiatry (1976)

The authors found that four measures of legal pressure were either unrelated or negatively related to retention and outcome in five drug abuse treatment modalities. This suggests that nonvolunteer clients are likely to be insufficiently motivated to benefit fully from treatment and their presence may adversely affect staff morale and prognosis of volunteer clients. The authors recommend that legal pressure not be used as a basis for assigning applicants to treatment modalities and suggest that treatment outcome might be improved by procedures that 1) deal clinically with motivational differences between volunteers and nonvolunteers, 2) establish stricter motivational criteria for admitting nonvolunteers, or 3) encourage enforcement of existing sanctions against violations of stipulations to treatment.
ESEN : une comparaison des programmes de vaccination - Première partie : la diphtérie
Authors: D Lévy-Bruhl, R G Pebody, I Veldhuijzen, M Valenciano, K Osborne
Journal: Eurosurveillance (1998)

L’objectif du Reseau Europeen de Surveillance Serologique ESEN (European Sero-Epidemiology Network) est de coordonner et d’harmoniser la surveillance serologique de l’immunite vis-a-vis des maladies evitables par la vaccination dans huit pays europeens (Danemark, Angleterre, France, Allemagne, Italie, Pays-Bas, Finlande et Suede). Mis en place en mars 1996 dans le cadre du programme Biomed II de la Communaute Europeenne, ce reseau est coordonne par le PHLS Communicable Disease Surveillance Centre (CDSC) a Londres.
Highly Effective New Treatments for Psoriasis Target the IL-23/Type 17 T Cell Autoimmune Axis
Authors: Jaehwan Kim, James G. Krueger
Journal: Annual Review of Medicine (2016)

Psoriasis vulgaris, affecting the skin, is one of the most common organ-specific autoimmune diseases in humans. Until recently, psoriasis was treated by agents or approaches discovered largely through serendipity. Many of the available drugs were inherently quite toxic when used as continuous treatment for many years in this chronic disease. However, an increasing understanding of disease-specific immune pathways has spurred development of pathway-targeted therapeutics during the past decade. Psoriasis is now the most effectively treated human autoimmune disease, with high-level clinical improvements possible in ∼90% of patients using a new generation of drugs that selectively target the IL-23/Type 17 T cell axis. Thus, psoriasis is a model for the success of a translational-medicine approach based on cellular and molecular dissection of disease pathogenesis in humans.
Deciding on Therapy: New Tools Factor In Cost of Care
Authors: Caroline McNeil
Journal: JNCI Journal of the National Cancer Institute (2016)

Last year saw the debut of five tools to help oncologists, patients, and policymakers decide on treatments for specific cancers.Coming from major clinical and policy organizations, the new tools, known generally as value frameworks, reflect oncology's move toward valuebased, patient-centered care.Although many cancer groups already have clinical guidelines and risk calculation tools to aid in decisionmaking, these go further: They compare treatment options directly, rating them on parameters such as efficacy and toxic effects.The tools also encourage and facilitate decisions based on patients' values and circumstances.But perhaps most groundbreaking is that they explicitly recognize financial cost as a factor in treatment decisions.The NCCN Evidence Blocks™, for instance, from the National Comprehensive Cancer Network, rate interventions in five areas.The first four categories-efficacy, safety, quality and quantity of evidence, and consistency of evidence-are familiar concepts, although they may not have been used to compare drugs so directly up to now.The fifth area, affordability, is brand new.Robert Carlson, M.D., NCCN's CEO, said cost was included to demystify the issue and make it easier for patients and physicians to discuss it openly."There's been a conspiracy of silence" on this issue, he said in a statement."Patients are embarrassed to bring up cost.Physicians hesitate to bring it up, because there's the implication that maybe if you can't afford it, you won't get the most effective treatment. . . .If patients are concerned about expense, and they see a therapy listed as very expensive, this is a signal to the patients and providers that it's time to understand the magnitude of the financial risk."
PD-008 Adding ramucirumab to second-line irinotecan, 5-fluorouracil and folinic acid (FOLFIRI) treatment for metastatic colorectal carcinoma (mCRC): resource utilization data from RAISE, a global, randomized, double-blind, multicenter phase 3 study
Authors: J. Kisro, A. Cohn, T. Yoshino, E. Van Cutsem, S. Hegewisch-Becker, F. Kullmann, P. Brück, A. Liepa, L. Yang, F. Nasroulah, J. Tabernero
Journal: Annals of Oncology (2016)
Phase III study of apatinib in advanced gastric cancer: A randomized, double-blind, placebo-controlled trial.
Authors: Shukui Qin
Journal: Journal of Clinical Oncology (2014)

4003 Background: Molecular targeted therapy has made great progress in the treatment of gastric cancer. This paper reports the outcome of a phase III clinical study of apatinib, as an oral small molecular of VEGFR-2 tyrosine kinase inhibitor, in the treatment of patients with advanced gastric cancer who prior failure to second-line chemotherapy. This study may provide a new treatment options and leading a new hope for these patients. Methods: This is a multicenter, randomized, double-blind, placebo-controlled phase 3 trial. Apatinib or matching placebo, 850 mg, po, qd, 28 days as one cycle. Primary outcomes were overall survival. Study randomization was centralized and stratified according to the number of metastatic sites (≤2 or >2). Planned to enroll 270 cases: 180 of apatinib and 90 of placebo. This trial was registered with ClinicalTrials.gov, number NCT01512745. Results: The patient baseline characteristics were similar in two arms in regards to age, historical of the disease, gender, ECOG scores, number of metastatic sites, pathological grading, clinical stage and therapy history(P>0.05). As the efficacy, median overall survival (mOS) was significantly prolonger in the apatinib group compare with in the placebo group (195 days versus 140 days ; HR= 0.71; 95% CI (0.54~0.94); p< 0.016). Median progression-free survival (mPFS) was also prolonged in the apatinib group compared with the placebo group (78 days versus 53 days, HR= 0.44, 95%CI (0.33~0.61), P<0.0001). The objective response rates (ORR) of apatinib group and placebo group were 2.84% and 0.00% respectively. As the safety, Treatment of apatinib group was generally well tolerated. Most of the adverse reaction could be managed by dose interruptions or reductions. Grade 3/4 adverse reactions that occurred in more than 2% of patients were hypertension, hand-and-foot syndrome, proteinuria, fatigue, anorexia, elevated aminotransferase. Conclusions: This study further confirmed the efficacy and safety of apatinib in the patients with advanced gastric cancer. 850 mg, qd is the recommended dose for clinical use. Clinical trial information: NCT01512745.
A Novel Strategy for Continuation ECT in Geriatric Depression: Phase 2 of the PRIDE Study
Authors: Charles H. Kellner, Mustafa M. Husain, Rebecca G. Knapp, W. Vaughn McCall, Georgios Petrides, Matthew V. Rudorfer, Robert C. Young, Shirlene Sampson, Shawn M. McClintock, Martina Mueller, Joan Prudic, Robert M. Greenberg, Richard D. Weiner, Samuel H. Bailine, Peter B. Rosenquist, Ahmad Raza, Styliani Kaliora, Vassilios Latoussakis, Kristen G. Tobias, Mimi C. Briggs, Lauren S. Liebman, Emma T. Geduldig, Abeba A. Teklehaimanot, Mary Dooley, Sarah H. Lisanby
Journal: American Journal of Psychiatry (2016)

The randomized phase (phase 2) of the Prolonging Remission in Depressed Elderly (PRIDE) study evaluated the efficacy and tolerability of continuation ECT plus medication compared with medication alone in depressed geriatric patients after a successful course of ECT (phase 1).PRIDE was a two-phase multisite study. Phase 1 was an acute course of right unilateral ultrabrief pulse ECT, augmented with venlafaxine. Phase 2 compared two randomized treatment arms: a medication only arm (venlafaxine plus lithium, over 24 weeks) and an ECT plus medication arm (four continuation ECT treatments over 1 month, plus additional ECT as needed, using the Symptom-Titrated, Algorithm-Based Longitudinal ECT [STABLE] algorithm, while continuing venlafaxine plus lithium). The intent-to-treat sample comprised 120 remitters from phase 1. The primary efficacy outcome measure was score on the 24-item Hamilton Depression Rating Scale (HAM-D), and the secondary efficacy outcome was score on the Clinical Global Impressions severity scale (CGI-S). Tolerability as measured by neurocognitive performance (reported elsewhere) was assessed using an extensive test battery; global cognitive functioning as assessed by the Mini-Mental State Examination (MMSE) is reported here. Longitudinal mixed-effects repeated-measures modeling was used to compare ECT plus medication and medication alone for efficacy and global cognitive function outcomes.At 24 weeks, the ECT plus medication group had statistically significantly lower HAM-D scores than the medication only group. The difference in adjusted mean HAM-D scores at study end was 4.2 (95% CI=1.6, 6.9). Significantly more patients in the ECT plus medication group were rated "not ill at all" on the CGI-S compared with the medication only group. There was no statistically significant difference between groups in MMSE score.Additional ECT after remission (here operationalized as four continuation ECT treatments followed by further ECT only as needed) was beneficial in sustaining mood improvement for most patients.
Patient-reported outcomes (PROs) from MARIANNE: A phase III study of trastuzumab emtansine (T-DM1) +/- pertuzumab (P) vs trastuzumab + taxane (HT) for HER2-positive advanced breast cancer.
Authors: Carlos H. Barrios, David Cella, Miguel Martin, Wolfgang Eiermann, Howard A. Burris, Young-Hyuck Im, Pier Franco Conte, Masakazu Toi, Tadeusz Pienkowski, Xavier B. Pivot, Benjamin Beckermann, Sven Franz Stanzel, Jennifer Petersen, Paul Anthony Ellis
Journal: Journal of Clinical Oncology (2016)

593 Background: MARIANNE (NCT01120184) is a randomized, phase III study of T-DM1 +/- P vs HT in pts with HER2-positive advanced breast cancer (BC). Methods: Pts with previously treated inoperable locally advanced BC or untreated metastatic BC were randomized 1:1:1 to HT, T-DM1+placebo or T-DM1+P. HRQoL (FACT-B-TOI-PFB), taxane-related symptoms (FACT-Taxane), and rates of nausea, diarrhea (FACT-C items) and alopecia (APA) were assessed. PROs were completed on day 1 of the first 8 cycles; the FACT-Taxane was also completed on day 8 of the first 2 cycles. To better assess treatment impact, a more frequent assessment schedule and additional instruments (FACT-Taxane, FACT-C items) were added in a protocol amendment. Data from this more detailed assessment are presented. Time to a clinically important difference (CID) from baseline (BL; ie, an event) and event incidence were estimated. All analyses are descriptive. Results: Of 1095 pts, 498 (HT: 173, T-DM1: 171, T-DM1+P: 154) randomized after the amendment completed both BL and ≥1 follow-up visit. No clear differences in BL characteristics were found between these pts and the ITT population. Pts with a CID in HRQoL, in neurotoxicity, and specific taxane-related symptoms are shown. Conclusions: Both T-DM1 arms reported a lower incidence of and a longer time to CID in neurotoxicity, as well as less alopecia vs HT. The T-DM1 arm also reported less nausea and diarrhea than the other arms. Consistent with these and other findings in the 1L setting, baseline HRQoL, measured by the FACT-B TOI-PFB, was maintained for a longer duration in T-DM1–treated vs HT-treated pts. Clinical trial information: NCT01120184. HT (n=173) T-DM1 (n=171) T-DM1+P (n=154) HRQoL deterioration Event,a % 67 53 51 Median time to event, mo (95% CI) 3.4 (2.5–4.2) 8.0 (3.7–18.9) 11.8 (4.1–21.8) FACT-Taxane: Neurotoxicity Event,b % 87 63 65 Median time to event, mo (95% CI) 2.1 (1.4–2.8) 6.2 (3.5–10.6) 4.2 (2.8–6.2) Alopecia, % BLc 14 13 13 C2D1 75 12 12 C3D1 85 11 16 C4D1 80 12 17 Diarrhea, % BLc 15 8 12 C1D8 35 18 35 C2D1 24 11 40 C2D8 34 8 41 Nausea, % BLc 22 14 21 C1D8 38 36 53 C2D1 27 21 36 C2D8 35 28 46 aCID = ≥5-point decrease from BL; bCID = ≥3-point increase in symptoms from BL; cBL = C1D1; C, cycle; D, day
PD-040 Risk assessment for gastrointestinal cancers in patients with family history of gastrointestinal cancer: Multi-center interim analysis study in the Republic of Korea
Authors: J.W. Chung, Y.J. Lim, S.M. Kim, J. Lee, J.-H. Han, Y.S. Kim, D.-S. Myung, D.K. Jang, S.P. Hong
Journal: Annals of Oncology (2016)
Gods from the machine of medicine
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2016)

Are you a god from the machine of medicine? Are you able to rapidly resolve once-insoluble problems? Does the government expect you to possess powers beyond your abilities? Do patients and other doctors expect the same? Do you, in turn, demand that colleagues are gods of all they survey, providing a difficult diagnosis or managing impending death? God from the machine, deus ex machina, allows us to appease our anxiety, argues Anthony Cohn, to take credit for success and abdicate responsibility for failure.1
NHS failed to commission mental health services properly at Yarl’s Wood
Authors: Anne Gulland
Journal: BMJ (2016)

Despite having more than a year to prepare, NHS England failed to commission mental health services that met the needs of vulnerable detainees at Yarl’s Wood immigration removal centre, a National Audit Office report has found.1

The report looked at the management arrangements between the NHS and G4S and between the Home Office and Serco at the Bedfordshire centre, which houses mainly women and children who are undergoing immigration assessment. The private security company G4S has run health services at the centre since September 2014, but responsibility for the contract ultimately lies with NHS England.

The report described many of the residents …
Surveillance de la résistance aux antituberculeux: les recommandations européennes
Authors: V Schwoebel, C S B Lambregts, M. L. Moro, F Drobniewski, S. E. Hoffner, M. C. Raviglione, H. L. Rieder
Journal: Eurosurveillance (2000)

Le controle de la tuberculose se heurte au probleme de la resistance aux antituberculeux, dont l’etendue en Europe reste mal connue. L’objectif des recentes recommandations europeennes sur la surveillance de la resistance aux antituberculeux, emises par un groupe de travail reunissant des representants de l’OMS, de l’IUATLD et de 35 pays de la Region Europe de l’OMS, est d’ameliorer la standardisation des definitions et des methodes. Elles mettent l’accent sur l’assurance de la qualite et sur la mise en relation des donnees de laboratoires et des donnees de declaration. A l’avenir, la surveillance de la resistance aux antituberculeux devrait faire partie integrante de la surveillance de la tuberculose.
Editorial practices of psychiatric and related journals: implications for women
Authors: E P Benedek
Journal: American Journal of Psychiatry (1976)

The author reports on the responses of 37 psychiatric and related professional journals to a questionnaire on procedures for selection of articles and of editors and/or editorial boards, with a focus on possible sexism in these practices. Results indicated little active effort to increase representation of women on editorial boards or in the authorship of journals, although existing practices were not necessarily discriminatory per se. The author hopes that this report will encourage more women to submit articles for publication and to seek active participation in the journals in their field.