tbuckley/cabot-search huggingface dataset:
Up-Regulation of Anti-Inflammatory, STAT3-Activating Hepatocyte Growth Factor and Interleukin-11 In Polycythemia Vera Is Independent of JAK2V617F and Contributes to the Growth of Clonal Erythroblasts
Authors: Marjorie Boissinot, Cedric Cleyrat, Mathias Vilaine, Yannick Jacques, Isabelle Corre, Sylvie Hermouet
Journal: Blood (2010)
GW26-e4667 Effect of Oxidatively Modified Low-Density Lipoprotein on Osteodifferentiation of Mesenchymal Stem Cells Co-cultured with Vascular Smooth Muscle Cells
Authors: Xiaochun Chen, C.H.E.N. Xiaochun, Hou Yu, Li Xiuling, Li Hanqing
Journal: Journal of the American College of Cardiology (2015)
HSP90 inhibition in HER2-positive breast cancer cells
Authors: Z. Qadir, J. Crown, M. R. Jensen, M. Clynes, D. Slamon, N. O'Donovan
Journal: Journal of Clinical Oncology (2009)

e14573 Background: HSP90 is required for the stability and activity of HER2 and downstream proteins, such as Akt, which play a key role in survival. We aimed to assess the anti-tumor effect of the HSP90 inhibitor NVP-AUY922 in HER-2 positive breast cancer cell lines. Methods: HER2 positive breast cancer cell lines with varied sensitivity to trastuzumab (Sensitive: BT474, SKBR3; acquired resistance: BT474Res, SKBR3Res; innate resistance: HCC1419, HCC1954, MDA-MB-453) were treated with the HSP90 inhibitor NVP-AUY922 (Novartis) and trastuzumab. IC 50 s were determined using the acid phosphatase assay. HER2, Akt and HSP90 levels were determined by immunoblotting after treatment with NVP-AUY922. Combinations of NVP-AUY922 with docetaxel, cisplatin and 5'-deoxy-5-fluorouridine (5-DFUR) were tested in BT474 and SKBR3 cells. Results: All of the HER2 positive cells were sensitive to NVP-AUY922, with IC 50 s ranging from 5.5 to 16.4 nM. Combined treatment with NVP-AUY922 (10 nM) and trastuzumab (10 nM) showed significantly greater inhibition of growth than either trastuzumab or NVP-AUY922 alone in BT474 and BT474Res cell lines (p&lt;0.005). In SKBR3 and SKBR3Res cells, dual treatment with NVP-AUY922 and trastuzumab did not significantly increase response compared to NVP-AUY922 alone ( Table 1 ). Treatment with NVP-AUY922 resulted in a dose-dependent decrease in HER2 and Akt levels in trastuzumab-sensitive and -resistant cells. Combinations of docetaxel, cisplatin or 5-DFUR with NVP- AUY922 were antagonistic in both BT474 and SKBR3 cells (CI values &gt;1). Conclusions: This study demonstrates that NVP-AUY922 has anti-tumor activity in trastuzumab-sensitive, and in both innate and acquired trastuzumab-resistant HER2 positive breast cancer cells. The antagonistic interactions observed for combinations of NVP-AUY922 with chemotherapy do not favour clinical evaluation of such combinations. However, combinations with other targeted therapies, such as trastuzumab, warrant further investigation. [Table: see text] [Table: see text]
Lenalidomide, Bortezomib, Pegylated Liposomal Doxorubicin, and Dexamethasone in Newly Diagnosed Multiple Myeloma: Updated Results of Phase I/II MMRC Trial.
Authors: Andrzej J. Jakubowiak, Donna E. Reece, Craig C. Hofmeister, Sagar Lonial, Todd M. Zimmerman, Erica L. Campagnaro, Robert L. Schlossman, Jacob Laubach, Noopur Raje, Tara Anderson, Kent Griffith, Melissa Hill, Colleen Harvey, Akari M. Dollard, Sandra Wear, Jennifer Barrickman, Craig Tendler, Dixie-Lee Esseltine, Susan L. Kelley, Mark S. Kaminski, Kenneth C. Anderson, Paul G. Richardson
Journal: Blood (2009)
Preliminary safety and efficacy of ruxolitinib in patients (pts) with primary and secondary myelofibrosis (MF) with platelet counts (PC) of 50–100x10<sup>9</sup>/L.
Authors: Moshe Talpaz, Solomon I. Hamburg, Katarzyna Jamieson, Howard R. Terebelo, Lawrence Afrin, Elliott F. Winton, Michael A. Scola, Roger M. Lyons, Jimmie Huling Harvey, Chris E. Holmes, Gregory L. Ortega, Josef T. Prchal, Richard T. Silver, Maria R. Baer, Susan Kay Erickson-Viitanen, Peter O'Neill, Wei Peng, Lance Leopold, Hagop Kantarjian, Srdan Verstovsek
Journal: Journal of Clinical Oncology (2012)

6630 Background: Ruxolitinib (RUX) has demonstrated clinical benefit as therapy for MF. This study explores the safety and efficacy of RUX in pts with MF and low PC, where clinical data are limited. Methods: In this phase II study, pts with intermediate-1 to high-risk MF, and PC of 50–100x10 9 /L started RUX at 5 mg BID. Doses could be increased in 5 mg QD increments every 4 weeks (wks) beginning at wk 4. Doses were decreased or held for PC &lt;35x10 9 /L and &lt;25x10 9 /L respectively. Assessments: Total Symptom Score (TSS, using the modified MF Symptom Assessment Form v2.0, and comprised of scores from 0=absent to 10=worst imaginable for night sweats, itching, bone/muscle pain, early satiety, abdominal discomfort and pain under left ribs); Patient Global Impression of Change (PGIC, a 7-point scale ranging from “very much improved” to “very much worse”); spleen size by palpation and by MRI (data not yet available); and safety. Results: At the time of analysis, 23 pts had completed ≥4 wks on study. At baseline: mean PC=72x10 9 /L; high (4%), intermediate-2 (52%) and intermediate-1 (44%) risk group; mean spleen length=16.6 cm; mean TSS=25.5. At the time of analysis, 4%, 40%, 26%, 26% and 4% of pts were receiving RUX 5 mg QD, 5 mg BID, 5 mg AM/10 mg PM, 10 mg BID, and 10 mg AM/15 mg PM, respectively. At wk 4 (all pts on 5 mg BID), mean TSS improved 14%; 13% had ≥50% improvement. At wk 8 (52% on 5 mg AM/10 mg PM), mean TSS improved 23%; 30% had ≥50% improvement. Mean spleen length reduction of 22% (wk 4) and 27% (wk 8) was observed, and PGIC scores of “much improved” or “very much improved” were reported in 35% (wk 4) and 39% (wk 8) of pts. There were no Grade 4 PC, no dose holds for AEs and no discontinuations; 1 pRBC transfusion-dependent pt had Grade 4 anemia. Three pts experienced a total of 4 SAEs (fever; hypnagogic dreams; and spleen pain/pneumonitis) which resolved while on treatment. Conclusions: Effects on spleen size, PGIC, and TSS, even over the first weeks at low doses, are superior to those observed in the placebo group in the COMFORT-I study. These preliminary findings suggest a dosing strategy starting with 5 mg BID RUX with subsequent dose optimization may be efficacious and well tolerated in MF pts who have low platelets.
Generation and Characterization of Microvesicles after Daratumumab Interaction with Myeloma Cells
Authors: Antonella Chillemi, Valeria Quarona, Andrea Zito, Fabio Morandi, Danilo Marimpietri, Massimiliano Cuccioloni, Oldham J Robert, Cragg S Mark, Marina Bolzoni, Denise Toscani, Vito Pistoia, Nicola Giuliani, Alberto L Horenstein, Kate Sasser, Fabio Malavasi
Journal: Blood (2015)
Improved Clinical Outcomes of High Risk β Thalassemia Major Patients Under Going a HLA Matched Related Allogeneic Stem Cell Transplant with the Use of a Treosulphan Based Conditioning Regimen and Peripheral Blood Stem Cell Grafts
Authors: Vikram Mathews, Biju George, Kavitha M Lakshmi, Aby Abraham, Rayaz Ahmed, Auro Viswabandhya, Alok Srivastava
Journal: Blood (2011)
GW26-e2456 Orphan Nuclear Receptor Nur77 deletion exacerbates low shear stress-induced carotid artery remodeling in mice
Authors: Ying Yu, Zhaohua Cai, Mingli Cui, Peng Nie, Zhe Sun, Shiqun Sun, Shichun Chu, Xiaolei Wang, Liuhua Hu, Jing Yi, Linghong Shen, Ben He
Journal: Journal of the American College of Cardiology (2015)
Idiopathic Pulmonary Fibrosis: The Association between the Adaptive Multiple Features Method and Fibrosis Outcomes
Authors: Margaret L. Salisbury, David A. Lynch, Edwin J. R. van Beek, Ella A. Kazerooni, Junfeng Guo, Meng Xia, Susan Murray, Kevin J. Anstrom, Eric Yow, Fernando J. Martinez, Eric A. Hoffman, Kevin R. Flaherty
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Adaptive multiple features method (AMFM) lung texture analysis software recognizes high-resolution computed tomography (HRCT) patterns.Objectives: To evaluate AMFM and visual quantification of HRCT patterns and their relationship with disease progression in idiopathic pulmonary fibrosis.Methods: Patients with idiopathic pulmonary fibrosis in a clinical trial of prednisone, azathioprine, and N-acetylcysteine underwent HRCT at study start and finish. Proportion of lung occupied by ground glass, ground glass–reticular (GGR), honeycombing, emphysema, and normal lung densities were measured by AMFM and three radiologists, documenting baseline disease extent and postbaseline change. Disease progression includes composite mortality, hospitalization, and 10% FVC decline.Measurements and Main Results: Agreement between visual and AMFM measurements was moderate for GGR (Pearson’s correlation r = 0.60, P < 0.0001; mean difference = −0.03 with 95% limits of agreement of −0.19 to 0.14). Baseline extent of GGR was independently associated with disease progression when adjusting for baseline Gender-Age-Physiology stage and smoking status (hazard ratio per 10% visual GGR increase = 1.98, 95% confidence interval [CI] = 1.20–3.28, P = 0.008; and hazard ratio per 10% AMFM GGR increase = 1.36, 95% CI = 1.01–1.84, P = 0.04). Postbaseline visual and AMFM GGR trajectories were correlated with postbaseline FVC trajectory (r = −0.30, 95% CI = −0.46 to −0.11, P = 0.002; and r = −0.25, 95% CI = −0.42 to −0.06, P = 0.01, respectively).Conclusions: More extensive baseline visual and AMFM fibrosis (as measured by GGR densities) is independently associated with elevated hazard for disease progression. Postbaseline change in AMFM-measured and visually measured GGR densities are modestly correlated with change in FVC. AMFM-measured fibrosis is an automated adjunct to existing prognostic markers and may allow for study enrichment with subjects at increased disease progression risk.
The Impact of Interferon-alpha2 on HLA-Genes in Patients with Polycythemia Vera and Related Neoplasms
Authors: Vibe Skov, Caroline H Riley, Mads Thomassen, Lasse Kjær, Thomas Stauffer Larsen, Morten K Jensen, Ole Weis Bjerrum, Torben A Kruse, Hans Carl Hasselbalch
Journal: Blood (2015)
GW26-e2921 Lack of association between CETP I405V Polymorphism and Lipid Levels and Longevity in Guangxi Hongshui River Basin
Authors: Lin Ge, Kaihui Yu, Yi Ding, Zhangya Bian, Lingjin Huang, Shanglin Pan, Junhua Peng
Journal: Journal of the American College of Cardiology (2015)
Australia backs down over jail terms for doctors who speak out about abuse of asylum seekers
Authors: Paul Smith
Journal: BMJ (2016)

The Australian government has changed controversial laws that threatened doctors with jail sentences if they spoke out about human rights abuses in the country’s immigration detention centres.

Australia’s offshore detention system has been under the international spotlight amid long running claims that detainees were living in tortuous conditions, subjected to physical and sexual abuse, as well as denied adequate medical care.1 2

Under the Australian Border Force Act introduced in June last year,3 anyone classed as an “entrusted person” working for, or on behalf of, the immigration detention system could be sentenced to two years’ imprisonment for making “unauthorised” disclosures about the situation faced by detainees.

Doctors for Refugees, an activist group, recently mounted …
Clonal evolution of chemotherapy-resistant urothelial carcinoma
Authors: Bishoy M Faltas, Davide Prandi, Scott T Tagawa, Ana M Molina, David M Nanus, Cora Sternberg, Jonathan Rosenberg, Juan Miguel Mosquera, Brian Robinson, Olivier Elemento, Andrea Sboner, Himisha Beltran, Francesca Demichelis, Mark A Rubin
Journal: Nature Genetics (2016)
Factors Involved in Response to Thalidomide in Myelodysplastic Syndrome: Impace of HLA and Prognostic Factors
Authors: Sule Mine Bakanay, Klara Dalva, Pervin Topcuoglu, Sinem Civriz-Bozdag, Mutlu Arat, Meral Beksac, Gunhan Gurman
Journal: Blood (2008)
A phase Ib trial of atacicept (TACI-Ig) to neutralize APRIL and BLyS in patients with refractory or relapsed B-cell chronic lymphocytic leukemia (B-CLL)
Authors: D. M. Kofler, T. Elter, A. Gianella-Borradori, S. Busby, C. M. Wendtner, M. Hallek
Journal: Journal of Clinical Oncology (2007)

3029 Background: B-CLL cells are resistant to apoptosis and thus exhibit prolonged survival and accumulation in vivo. Exogenously added soluble BLyS (B-Lymphocyte Stimulator) and APRIL (A PRoliferation-Inducing Ligand) have been shown to protect B-CLL cells from apoptosis in vitro. Nurse-like cells derived in vitro from CLL patients express high levels of APRIL and BLyS and thereby support CLL cell survival. Inhibition of APRIL significantly reduces CLL viability in vitro, indicating an important role for APRIL in this setting. Methods: This is an open-label, dose-escalation phase I trial to assess the safety, pharmacokinetics and biological effects of atacicept administered intravenously once weekly for 5 weeks to patients with refractory or relapsed B-CLL. Eligible patients are being enrolled in sequential cohorts of 3 to receive atacicept at 1, 4, 10, 15, 20 or 27 mg/kg. Evaluation of response is being assessed using NCI-WG criteria. Results: Preliminary results of the first 4 cohorts of the dose-escalation study are reported. Twelve CLL patients have entered the trial. No dose limiting toxicity has been observed and no SAE related to study drug has been reported to date. One case of mild nausea is the only drug-related toxicity reported to date. Three of six patients treated with 10 mg/kg and 15 mg/kg experienced a stabilization of their disease during the treatment period; prior to start of atacicept treatment, all had rapidly increasing leukocyte counts. One of these patients (10 mg/kg cohort), who was refractory to fludarabine therapy, has had stable disease according to NCI-WG criteria for over six months and is still receiving atacicept treatment. This same patient had a slight decrease (approximately 14% change from baseline) in absolute CLL cell concentration by Day 29 before final dosing. At lower dose levels all patients demonstrated progressive disease. Conclusions: Treatment with atacicept was well tolerated at the dose levels tested so far. The multiple cases of disease stabilization at higher dose levels in this heavily pre-treated patient population are promising, and support further study with atacicept in CLL. Accrual of patients at higher dose levels is ongoing. No significant financial relationships to disclose.
Reducing Stroke Disability
Authors: Rebecca Voelker
Journal: JAMA (2016)

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Nephrology Crossword: Antihypertensive agents
Authors: Manish Saha, Kenar D. Jhaveri
Journal: Kidney International (2016)

3.A major side effect of large doses of furosemide6.Metolazone in the serum is bound to albumin and this cell (abbr.)7.This antihypertensive medication has a uricosuric effect8.Amiloride is excreted into the tubule through organic-______ pathways10.This electrolyte abnormality needs to be corrected before initiation of acetazolamide11.More than 95% of metolazone is eliminated from the body in ______ hours13.Spironolactone can alter the clearance of this antiarrhythmic 1.Its action on the ENaC results in sodium retention; a possible mechanism for edema in nephrotic syndrome2.This diuretic doesn’t need to be secreted into tubules to provide its effect3.This antihypertensive agent can cause kidney injury by causing vasoconstriction, interstitial nephritis, and crystal formation4.This loop diuretic has more predictable pharmacokinetics than furosemide5.This hypertension trial (acronym) showed that chlorthalidone may improve cardiovascular outcomes8.Short-term tolerance of diuretics is called ______9.Alternative diuretic in patients with sulfa anaphylaxis10.Compound of this metal was a potent diuretic prior to the use of thiazides and loop diuretics (abbr.)12.Below this level of serum albumin (g/dl), combined infusion of albumin and a loop diuretic may enhance diuresis in nephrotic syndrome All the authors declared no competing interests.
Quality of life (QoL) in patients with malignant dysphagia: An international randomized trial comparing radiotherapy alone (RT) versus chemoradiotherapy (CRT)—TROG03.01 NCICCTG ES2.
Authors: Rebecca Wong, Heather-Jane Au, Keyue Ding, Jennifer A Harvey, Sonya Stephens, Christopher J. O'Callaghan, Andrew Kneebone, Sam Ngan, Iain G. Ward, Rajarshi Roy, Thomas Richard Sullivan, Tirath Nijjar, James Joseph Biagi, Michael Gordon Penniment
Journal: Journal of Clinical Oncology (2014)

163 Background: The dominant symptom for pts with esophageal cancer is dysphagia. Palliative radiotherapy is commonly employed for symptom relief. We report the effect on QoL in our study comparing a 2-3 week course of RT alone vs the same RT with a single cycle of concomitant CT. Methods: 220 pts with malignant dysphagia were randomized to receive RT (30-35Gy in 10-15 fr) (n=109) ± concomitant CT (5FU and cisplatin D1-4) cycle. The primary outcome was dysphagia relief. QoL was evaluated using EORTC QLQ30/OES18 at baseline, wk 9, 13 and mthly x1yr. Group mean scores were compared between arms using Wilcoxon Rank-Sum test. Proportion of pts with improved, stable or worsened QoL (≥10 point change at any time compared with baseline) using chi square and MH chi-square test (for trend), while time to dysphagia improvement was compared using K-M estimates. Results: QoL compliance ranged from 77% (169/220) at baseline to 62% (36/58) at mth12 and was similar between groups. Baseline mean scores were equivalent between arms with the exception of physical [79 (SD19) CRT vs. 83.84 (SD19) RT; p=0.016] and role domains [61 (SD34) CRT vs. 72 (SD32) RT; p = 0.01]. There was no significant difference in QoL between the arms. The proportion of pts with improvement in the dysphagia domain was 50% CRT vs 64% RT (ns) while the time to improvement was 2.6m CRT vs 2.3m RT (ns). The eating domain was improved in 68% CRT and 74% RT (ns) while global QoL was 46% in both arms. Other symptom domains/items that were improved in more than half of the pts included 62% in pain and 52% in appetite. Functional domain improvements were moderate ranging from 41% emotional, 39% role, 38% social, 28% cognitive to 18% physical (average of scores in both arms). Conclusions: QoL data showed improvement in domains associated with nutritional intake for 50-70% of pts depending on the symptom measured. This was accompanied by moderate improvement in functional domains. No significant benefit was observed when CT was added to RT alone. Clinical trial information: NCT00193882.
Increased Risk of Incident Chronic Kidney Disease, Cardiovascular Disease, and Mortality in Patients With Diabetes With Comorbid Depression
Authors: Marta Novak, Istvan Mucsi, Connie M. Rhee, Elani Streja, Jun L. Lu, Kamyar Kalantar-Zadeh, Miklos Z. Molnar, Csaba P. Kovesdy
Journal: Diabetes Care (2016)

OBJECTIVE It is not known if patients with diabetes with depression have an increased risk of chronic kidney disease (CKD). We examined the association between depression and incident CKD, mortality, and incident cardiovascular events in U.S. veterans with diabetes. RESEARCH DESIGN AND METHODS Among a nationally representative prospective cohort of &amp;gt;3 million U.S. veterans with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2, we identified 933,211 patients with diabetes. Diabetes was ascertained by an ICD-9-CM code for diabetes, an HbA1c &amp;gt;6.4%, or receiving antidiabetes medication during the inclusion period. Depression was defined by an ICD-9-CM code for depression or by antidepressant use during the inclusion period. Incident CKD was defined as two eGFR levels &amp;lt;60 mL/min/1.73 m2 separated by ≥90 days and a &amp;gt;25% decline in baseline eGFR. The associations between depression and outcomes were assessed using Cox proportional regression. RESULTS Depression was present in 340,806 patients at enrollment. Depressed patients were younger (61 ± 11 vs. 65 ± 11 years), had higher eGFR (84 ± 15 vs. 81 ± 14 mL/min/1.73 m2), but had more comorbidities. Incident CKD developed in 180,343 patients. Depression was associated with 20% higher risk of incident CKD (adjusted hazard ratio [aHR] and 95% CI: 1.20 [1.19–1.21]). Similarly, depression was associated with increased all-cause mortality (aHR and 95% CI: 1.25 [1.24–1.26]). CONCLUSIONS The presence of depression in patients with diabetes is associated with higher risk of developing CKD compared with nondepressed patients. Intervention studies should determine if effective treatment of depression in patients with diabetes would prevent major renal and cardiovascular complications.
GW26-e2407 Protective Effects of Dihydromyricetin and Myricetin against Myocardial Ischemia/Reperfusion Injury In Vivo and In Vitro
Authors: Yong Ye, Xianhong OU, Qiujie Huang, Huagang Liu, Yonghong Liang, Yefei Yuan, Yunfei Song, Xiaorong Zeng
Journal: Journal of the American College of Cardiology (2015)
Childhood Socioeconomic Status in Predicting Metabolic Syndrome and Glucose Abnormalities in Adulthood: The Cardiovascular Risk in Young Finns Study
Authors: Elina Puolakka, Katja Pahkala, Tomi T. Laitinen, Costan G. Magnussen, Nina Hutri-Kähönen, Päivi Tossavainen, Eero Jokinen, Matthew A. Sabin, Tomi Laitinen, Marko Elovainio, Laura Pulkki-Råback, Jorma S.A. Viikari, Olli T. Raitakari, Markus Juonala
Journal: Diabetes Care (2016)

We prospectively examined whether family socioeconomic status (SES) in childhood is associated with metabolic syndrome (MetS), impaired fasting glucose (IFG), or type 2 diabetes in adulthood.The sample comprised 2,250 participants from the longitudinal Cardiovascular Risk in Young Finns Study cohort. Participants were 3-18 years old at baseline (mean age 10.6 years), and they were followed for 31 years. SES was characterized as reported annual income of the family and classified on an 8-point scale.For each 1-unit increase in family SES in childhood, the risk for adult MetS decreased (risk ratio [95% confidence interval] 0.94 [0.90-0.98]; P = 0.003) when adjusted for age, sex, childhood cardiometabolic risk factors (lipids, systolic blood pressure, insulin, and BMI), childhood physical activity, and fruit and vegetable consumption. The association remained after adjustment for participants' own SES in adulthood (0.95 [0.91-0.99]; P = 0.005). A similar association was seen between childhood SES and the risk of having either adult IFG or type 2 diabetes (0.96 [0.92-0.99]; P = 0.01, age and sex adjusted). This association became nonsignificant after adjustment for childhood risk factors (P = 0.08). Of the individual components of MetS, lower SES in childhood predicted large waist circumference (0.96 [0.93-0.99]; P = 0.003) and a high triglycerides concentration (0.96 [0.92-1.00]; P = 0.04) after adjustment for the aforementioned risk factors.Lower SES in childhood may be associated with an increased risk for MetS, IFG, and type 2 diabetes in adulthood. Special attention could be paid to children of low SES families to decrease the prevalence of MetS in adulthood.