tbuckley/cabot-search huggingface dataset:
Sexual behavior and dysfunction following treatment of gynecologic malignancies.
Authors: D. M. Chase, K. Osann, L. B. Wenzel, U. Gujral, V. J. Speir, K. S. Tewari
Journal: Journal of Clinical Oncology (2010)

e19502 Background: Preservation of sexual function has important quality of life (QoL) ramifications. The objective of this study was to document the characteristics of sexual dysfunction in a heterogeneous sample of gynecologic cancer survivors. Methods: Eligible patients were those presentinig consecutively to a Gynecologic Oncology clinic over an 8 month period. Patients consented to complete validated sexual behavior instruments. A survey regarding counseling on sexual rehabilitation was also included. Statistical tests used to analyze the data included t-test and chi- square. Results: 110 patients elected to complete at least one of the surveys. The median age was 53 years (range 24-84). Of the 73 patients who had a partner, 43 (59%) patients had sexual relations over the last month. Overall, one-third of patients reported that they have less interest in sexual activity since cancer diagnosis. Younger women were more sexually active (p<0.03). Women who did not receive chemotherapy (p=0.04) or radiation (p=0.11) were also more sexually active. Younger patients scored higher on the sexual interest (SI) scale than the older patients (p<0.005). Very few women (n=15) reported that their doctor had discussed sexual function with them, with younger patients demonstrating more interest in being informed (p=0.01). Women with the diagnosis of cervical cancer, earlier stages, married, and white women, expressed preference toward education on sexual function although this was not statistically significant. The mean score of correct answers on the Sexual Knowledge Questionnaire was 72% (25-100%), with younger age and white ethnicity associated with higher scores (p=0.02). Knowledge was lower for cervical and ovarian cancer patients but this was not statistically significant. Conclusions: Sexual health among women with gynecologic malignancies may be compromised due to direct involvement by the cancer and/or through damage induced by various treatment modalities. In this descriptive study, the need for improving sexual education and documenting dysfunction is implicit. A larger sample size may identify patients at particularly high risk for sexual dysfunction who can then be triaged for targeted interventions. No significant financial relationships to disclose.
Long-term safety of lenalidomide (LEN) in relapsed/refractory multiple myeloma (RRMM) patients (Pts): Analysis of pooled data.
Authors: B. G. Durie, G. Morgan, J. F. San-Miguel, R. Z. Orlowski, S. Lonial, R. Niesvizky, Z. Yu, K. C. Anderson
Journal: Journal of Clinical Oncology (2011)

8086 Background: LEN has significantly extended RRMM pt survival. Given extended pt survival and known association of aging with the development of malignancies, the incidence of second primary malignancies (SPM) observed in LEN studies was compared with expected background incidence of all invasive cancers as reported from the U.S. Surveillance, Epidemiology, and End Results (SEER) Cancer Registries, 2003-2007. Methods: Pooled data from LEN-based treatment arms of 11 Celgene sponsored studies in which RRMM pts received ≥24 months (mos) of LEN were analyzed for SPM incidence and incidence rate (IR) per 100 person-yrs (PY). By SEER definition, non-melanoma skin cancers and in situ malignancies were excluded. Results: 3,839 pts were included in this retrospective analysis. Median age at study entry was 64 (interquartile range 29-92). Treatment included single-agent LEN (n = 729; 19.1%) and LEN + dexamethasone (n = 3,083; 80.9%). Median LEN treatment duration was 5 mos (range 0.03-58.27) with 313 (8.2%) pts receiving ≥24 mos of treatment. A total of 57 SPMs were identified (8 myelodysplastic syndromes [MDS], 1 acute myeloid leukemia [AML], 2 B-cell malignancies, 46 solid tumors). Of these, 22/313 (7%) were in pts with ≥24 mos of LEN treatment (4 MDS, 1 AML, 17 solid tumors). Overall SPM IR was 2.35 for ≥24 mos of treatment. The standardized incidence ratio (SIR) was 0.77 (CI 0.43 – 1.28). These rates compare favorably with IR for all invasive cancers reported from SEER (range 1.3-2.2 per 100 PY for all persons ages 60-85+). Conclusions: Treatment with LEN-based therapy for RRMM, including treatment durations of ≥24 mos, with clear clinical benefit and no significant increase in rate of SPM compared to incidence rates for invasive malignancies reported by SEER. Pt characteristics No. of cases (SPM IR per 100 PY) Age, yrs <65 (n = 2,060) 19 (1.27) 65-75 (n = 1,335) 32 (3.71) >75 (n = 444) 6 (2.46) Cumulative LEN dose received, mg (n = 3,812)* <2400 15 (3.50) ≥2400 41 (1.89) Treatment duration, mos <12 / ≥12 26 (2.29) / 31 (2.12) <18 / ≥18 32 (2.25) / 25 (2.13) <24 / ≥24 35 (2.10) / 22 (2.35) Initial regimen Single-agent LEN (N = 731) 19 (2.42) LEN + DEX (N = 3,108) 38 (2.09) * Cumulative dose for 27 pts was incalculable due to missing data.
Elevated local [Ca<sup>2+</sup>] and CaMKII promote spontaneous Ca<sup>2+</sup>release in ankyrin-B-deficient hearts
Authors: Iuliana Popescu, Samuel Galice, Peter J. Mohler, Sanda Despa
Journal: Cardiovascular Research (2016)

Loss-of-function mutations in the cytoskeletal protein ankyrin-B (AnkB) cause ventricular tachyarrhythmias in humans. Previously, we found that a larger fraction of the sarcoplasmic reticulum (SR) Ca 2+ leak occurs through Ca 2+ sparks in AnkB-deficient (AnkB +/− ) mice, which may contribute to arrhythmogenicity via Ca 2+ waves. Here, we investigated the mechanisms responsible for increased Ca 2+ spark frequency in AnkB +/− hearts. Using immunoblots and phospho-specific antibodies, we found that phosphorylation of ryanodine receptors (RyRs) by CaMKII is enhanced in AnkB +/− hearts. In contrast, the PKA-mediated RyR phosphorylation was comparable in AnkB +/− and wild-type (WT) mice. CaMKII inhibition greatly reduced Ca 2+ spark frequency in myocytes from AnkB +/− mice but had little effect in the WT. Global activities of the major phosphatases PP1 and PP2A were similar in AnkB +/− and WT hearts, while CaMKII autophosphorylation, a marker of CaMKII activation, was increased in AnkB +/− hearts. Thus, CaMKII-dependent RyR hyperphosphorylation in AnkB +/− hearts is caused by augmented CaMKII activity. Intriguingly, CaMKII activation is limited to the sarcolemma–SR junctions since non-junctional CaMKII targets (phospholamban, HDAC4) are not hyperphosphorylated in AnkB +/− myocytes. This local CaMKII activation may be the consequence of elevated [Ca 2+ ] in the junctional cleft caused by reduced Na + /Ca 2+ exchange activity. Indeed, using the RyR-targeted Ca 2+ sensor GCaMP2.2-FBKP12.6, we found that local junctional [Ca 2+ ] is significantly elevated in AnkB +/− myocytes. The increased incidence of pro-arrhythmogenic Ca 2+ sparks and waves in AnkB +/− hearts is due to enhanced CaMKII-mediated RyR phosphorylation, which is caused by higher junctional [Ca 2+ ] and consequent local CaMKII activation.
Long-acting octreotide for the treatment of symptoms of bowel obstruction in advanced ovarian cancer
Authors: R. T. Penson, C. N. Krasner, M. V. Seiden, T. Atkinson, A. Kornblith, S. Campos, A. Klein, U. Matulonis
Journal: Journal of Clinical Oncology (2005)

5159 Background: Symptoms of bowel obstruction and intermittent chronic obstruction are common complications in patients (pts) with recurrent ovarian cancer. Mechanisms of bowel obstructions include intraabdominal carcinomatosis, drug-induced intestinal immobility, and intraluminal obstruction. Octreotide inhibits gastrointestinal hormonal secretion and decreases splanchnic blood flow. Sandostatin LARDepot (LAR) is a long-acting depot form of octreotide given intramuscularly (IM) once per month. Methods: The objectives of this trial were to assess efficacy and toxicities of LAR in ovarian cancer pts with chronic or intermittent bowel obstruction. Pts must have recurrent ovarian or primary peritoneal cancer, symptoms related to a non-surgically amenable bowel obstruction, and a life expectancy of >2 months. Following a test dose of short-acting octreotide to rule out a hypersensitivity reaction, subcutaneous (SQ) octreotide was started at a dose of 100 mcg 3x/day for 2 weeks (in order to quickly achieve therapeutic serum levels) along with LAR 30 mg IM qmonth. IM LAR was given until symptom progression or toxicity. Results: Since the study began in 9/02, 15 pts have been enrolled, and the study is now completed. The mean age of pts is 57 years of age. One enrolled pt never received any study drug, and data is available on 14 pts. Of the 15 pts enrolled, 13 have died from cancer progression. 3 pts received a successful test dose and one LAR injection, but were taken off study per their request. Of the 9 pts who received >2 months of LAR, the duration of LAR ranged from 2 to >12 months with a median of 4 months. No grade 3 or 4 toxicities related to LAR were seen, and LAR was well tolerated. 2 pts had skin reactions, and 1 of these 2 pts was taken off study. QOL data was collected and will be presented at ASCO. Conclusions: LAR is well tolerated following successful administration of a test dose of SQ octreotide. In this ovarian cancer population with inoperable bowel obstruction, LAR has activity in the management of symptoms of bowel obstruction and can be used safely in this population without apparent cumulative toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis
microRNAs in the Same Clusters Evolve to Coordinately Regulate Functionally Related Genes
Authors: Yirong Wang, Junjie Luo, Hong Zhang, Jian Lu
Journal: Molecular Biology and Evolution (2016)

MicroRNAs (miRNAs) are endogenously expressed small noncoding RNAs. The genomic locations of animal miRNAs are significantly clustered in discrete loci. We found duplication and de novo formation were important mechanisms to create miRNA clusters and the clustered miRNAs tend to be evolutionarily conserved. We proposed a “functional co-adaptation” model to explain how clustering helps newly emerged miRNAs survive and develop functions. We presented evidence that abundance of miRNAs in the same clusters were highly correlated and those miRNAs exerted cooperative repressive effects on target genes in human tissues. By transfecting miRNAs into human and fly cells and extensively profiling the transcriptome alteration with deep-sequencing, we further demonstrated the functional co-adaptation between new and old miRNAs in the miR-17–92 cluster. Our population genomic analysis suggest that positive Darwinian selection might be the driving force underlying the formation and evolution of miRNA clustering. Our model provided novel insights into mechanisms and evolutionary significance of miRNA clustering.
Government must follow the evidence before implementing seven day GP services
Authors: Anne Gulland
Journal: BMJ (2016)

The government should ensure that there is a real demand for weekend access to general practice before imposing seven day services nationally, MPs have said.

In a wide ranging report on primary care1 the health select committee said that there needed to be a full evaluation of the pilot programmes—that tested the provision of routine weekend appointments—“before any new system was rolled out around the country.”

The report continued, “The government’s approach should be evidence based, learn from best practice, and avoid unintended consequences such as damaging weekday …
Case 10-1981
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Gilbert H. Daniels, James J. Galdabini
Journal: New England Journal of Medicine (1981)

Presentation of CaseA 47-year-old woman was admitted to the hospital because of abdominal pain and weight loss.She was well until four months earlier, when she began to have crampy pain in the epigastrium that was unrelated to the ingestion of food and often awakened her during the night. Her lifelong constipation worsened. Two months before admission she noticed a bitter taste and xerostomia, accompanied by anorexia, weakness, and fatigue. Polydipsia, polyuria, and nocturia developed, with night sweats, photophobia, and pedal edema. Six weeks before entry she began to have difficulty in arising from a chair or climbing stairs, . . .
REF6 recognizes a specific DNA sequence to demethylate H3K27me3 and regulate organ boundary formation in Arabidopsis
Authors: Xia Cui, Falong Lu, Qi Qiu, Bing Zhou, Lianfeng Gu, Shuaibin Zhang, Yanyuan Kang, Xiekui Cui, Xuan Ma, Qingqing Yao, Jinbiao Ma, Xiaoyu Zhang, Xiaofeng Cao
Journal: Nature Genetics (2016)
Monitoring Minimal Residual Disease in Acute Myeloid Leukemia: Ready for Prime Time?
Authors: Farhad Ravandi, Jeffrey L. Jorgensen
Journal: Journal of the National Comprehensive Cancer Network (2012)

Predicting the outcome of therapy in patients with acute myeloid leukemia (AML) is currently necessary for making treatment decisions. Pretreatment covariates, such as clinical and molecular predictors, have helped identify which patients are more or less likely to survive their disease using the currently available regimens. Progress in establishing optimized flow cytometry and quantitative polymerase chain reaction assays for detecting minimal residual leukemia has provided new potential tools for predicting outcome. However, the most important next step in using these techniques toward personalized treatment of AML would be developing effective and safe strategies for eradicating the residual leukemic cells that are likely chemoresistant. With further refinement and standardization of the assays, and the development of novel, effective, and molecularly targeted agents, monitoring of minimal residual disease is likely to be incorporated into AML guidelines.
Evaluation of the thrombospondin-1 analogue ABT-510 in the APC<sup>Min/+</sup> mouse intestinal adenoma model
Authors: D. E. Joyce, G. Mulji, L. S. Gutierrez, F. J. Castellino
Journal: Journal of Clinical Oncology (2006)

13545 Background: The extracellular matrix protein Thrombospondin-1 (TSP-1) affects the angiogenic balance in cancer to suppress tumor growth. Exogenous TSP-1 or the peptide derivative ABT-510 (Abbott, Chicago, IL) can reverse this angiogenic switch from adenoma to carcinoma. We evaluated treatment effects of ABT-510 in the APC Min/+ mouse spontaneous intestinal adenoma model. This study determined reduction in intestinal adenoma number after ABT-510 or the combined treatment of ABT-510/bevacizumab (Genentech) compared to no treatment in APC Min/+ . Proliferation, vascularity, and dysplasia were also compared. Methods: 90 day old APC Min/+ mice (familial adenomatous polyposis, 5q21 termination), Jackson Laboratory (Bar Harbor, ME)) received drug for three weeks: 1.) ABT-510, 60 mg/Kg/day s.c. pump for 2 weeks then i.p. daily for the last 7 days, 2.) Anti-VEGF antibody bevacizumab 10 mg/Kg i.p. twice per week in combination with ABT-510, and 3.) untreated controls. After 21 days mice were sacrificed, intestines harvested and adenomas enumerated. Immunohistochemistry (PCNA, vWF/CD31) was performed. Studies were IACUC approved. Wilcoxon signed-rank test was used to compare results. Results: Twenty one mice were evaluated with no adverse effects. Comparisons were made to untreated APC Min/+ controls. Untreated controls (N=7) demonstrated a mean of 7.7±1.25 polyps. ABT-510 treated APC Min/+ (N=8) demonstrated a mean of 3.4±1.8 polyps, significantly different from controls (p&lt;0.004). Combined bevacizumab and ABT-510 treatment demonstrated a mean of 4.7 ±3.0 polyps (p&lt;0.008). There was no significant difference between the ABT-510 and combined ABT-510/bevacizumab treated groups. Immunohistochemistry for tumor vascularity (anti-CD31/anti-vWF) and for proliferation (PCNA) demonstrated enhanced vascular and PCNA staining in polyps, but no differences were detected in tumor dysplasia or immunohistochemistry compared across control and treatment groups. Conclusions: Significant reduction in APC Min/+ polyp number was seen with ABT-510 and the combination ABT-510/bevacizumab treatment groups compared to untreated controls. Tumor-specific vascularity and proliferation was characteristically no different across control and treated groups. [Table: see text]
69P Intratumoral heterogeneity of HER2 expression is associated with malignant biological behavior
Authors: M. Hosonaga, E. Sato, K. Yamada, H. Kaise, F. Kimura, Y. Kawai, A. Ueda, S. Teraoka, M. Okazaki, T. Ishikawa
Journal: Annals of Oncology (2015)
Increasing The Dose Of AraC In Consolidation Therapy Does Not Lead To Higher Overall Survival Or Improved Relapse Incidence In Patients With AML Over The Age Of 60 Years
Authors: Dietger Niederwieser, Rainer Krahl, Christian Jakob, Thomas Heinicke, Christoph Kahl, Antje Schulze, Hans-Heinrich Wolf, Bernhard Opitz, Ute Kreibich, Frank Rothmann, Christian Junghanss, Detlev Haehling, Manfred Schulze, Norma Peter, Ute Hegenbart, Haifa Kathrin Al-Ali, Carsten Hirt, Wolfram Poenisch, Thoralf Lange, Simone Heyn, Vladan Vucinic, Kristina Bartsch, Thomas Fischer, Georg Maschmeyer, Andreas Hochhaus
Journal: Blood (2013)
Sex steroid deficiency–associated bone loss is microbiota dependent and prevented by probiotics
Authors: Jau-Yi Li, Benoit Chassaing, Abdul Malik Tyagi, Chiara Vaccaro, Tao Luo, Jonathan Adams, Trevor M. Darby, M. Neale Weitzmann, Jennifer G. Mulle, Andrew T. Gewirtz, Rheinallt M. Jones, Roberto Pacifici
Journal: Journal of Clinical Investigation (2016)

A eubiotic microbiota influences many physiological processes in the metazoan host, including development and intestinal homeostasis. Here, we have shown that the intestinal microbiota modulates inflammatory responses caused by sex steroid deficiency, leading to trabecular bone loss. In murine models, sex steroid deficiency increased gut permeability, expanded Th17 cells, and upregulated the osteoclastogenic cytokines TNFα (TNF), RANKL, and IL-17 in the small intestine and the BM. In germ-free (GF) mice, sex steroid deficiency failed to increase osteoclastogenic cytokine production, stimulate bone resorption, and cause trabecular bone loss, demonstrating that the gut microbiota is central in sex steroid deficiency–induced trabecular bone loss. Furthermore, we demonstrated that twice-weekly treatment of sex steroid–deficient mice with the probiotics Lactobacillus rhamnosus GG (LGG) or the commercially available probiotic supplement VSL#3 reduces gut permeability, dampens intestinal and BM inflammation, and completely protects against bone loss. In contrast, supplementation with a nonprobiotic strain of E. coli or a mutant LGG was not protective. Together, these data highlight the role that the gut luminal microbiota and increased gut permeability play in triggering inflammatory pathways that are critical for inducing bone loss in sex steroid–deficient mice. Our data further suggest that probiotics that decrease gut permeability have potential as a therapeutic strategy for postmenopausal osteoporosis.
Concern over arsenic in infants’ rice products rises after US study
Authors: Jacqui Wise
Journal: BMJ (2016)

Infants who ate rice or rice products had higher concentrations of arsenic in their urine than those who did not, US research published in JAMA Pediatrics has found.1 However, stricter controls on arsenic in rice products in the European Union mean that this is less likely to be a problem in the United Kingdom.

The study included 759 infants in New Hampshire who were followed up every four months until 12 months of age. At 12 months, dietary patterns from the past week were assessed. The researchers found that 80% of the infants had been introduced to rice cereal in the first year of life, 64% starting at 4 …
Phosphodiesterase Type 5 Inhibition Reduces Albuminuria in Subjects with Overt Diabetic Nephropathy
Authors: Wim Scheele, Susan Diamond, Jeremy Gale, Valerie Clerin, Nihad Tamimi, Vu Le, Rosalind Walley, Fernando Grover-Páez, Christelle Perros-Huguet, Timothy Rolph, Meguid El Nahas
Journal: Journal of the American Society of Nephrology (2016)

Diabetic nephropathy (DN) is the leading cause of ESRD worldwide. Reduced bioavailability or uncoupling of nitric oxide in the kidney, leading to decreased intracellular levels of the nitric oxide pathway effector molecule cyclic guanosine monophosphate (cGMP), has been implicated in the progression of DN. Preclinical studies suggest that elevating the cGMP intracellular pool through inhibition of the cGMP-hydrolyzing enzyme phosphodiesterase type 5 (PDE5) might exert renoprotective effects in DN. To test this hypothesis, the novel, highly specific, and long-acting PDE5 inhibitor, PF-00489791, was assessed in a multinational, multicenter, randomized, double-blind, placebo-controlled, parallel group trial of subjects with type 2 diabetes mellitus and overt nephropathy receiving angiotensin converting enzyme inhibitor or angiotensin receptor blocker background therapy. In total, 256 subjects with an eGFR between 25 and 60 ml/min per 1.73 m 2 and macroalbuminuria defined by a urinary albumin-to-creatinine ratio &gt;300 mg/g, were randomly assigned 3:1, respectively, to receive PF-00489791 (20 mg) or placebo orally, once daily for 12 weeks. Using the predefined primary assessment of efficacy (Bayesian analysis with informative prior), we observed a significant reduction in urinary albumin-to-creatinine ratio of 15.7% (ratio 0.843; 95% credible interval 0.73 to 0.98) in response to the 12-week treatment with PF-00489791 compared with placebo. PF-00489791 was safe and generally well tolerated in this patient population. Most common adverse events were mild in severity and included headache and upper gastrointestinal events. In conclusion, the safety and efficacy profile of PDE5 inhibitor PF-00489791 supports further investigation as a novel therapy to improve renal outcomes in DN.
TCTAP C-029 Stand-alone Thrombus Aspiration in Acute Coronary Syndrome Due to Coronary Artery Ectasia
Authors: Hendro Adi Kuncoro, Soetandar Widjaja, Iman Suhartono, Andreas Sumargo, Johan Senihardja, Yosua Arthur Iskandar, Monique Priscilla Fransiska Rotty, Benny Mulyanto Setiadi, Bambang Budiono, Janry Anton Pangemanan, Agnes Lucia Panda, Edmond Jim
Journal: Journal of the American College of Cardiology (2016)
P0715 : Steady-state pharmacokinetics and safety of coadministration of pan-genotypic, direct acting protease inhibitor, ABT-493 with pan-genotypic NS5A inhibitor, ABT-530, in healthy adult subjects
Authors: C.-W. Lin, W. Liu, A. Asatryan, A. Campbell, W. Zhao, H. Wang, D. Sidhu, J. Clifton, J. Kort, S. Dutta
Journal: Journal of Hepatology (2015)
Pluronic P85-coated poly(butylcyanoacrylate) nanoparticles overcome phenytoin resistance in P-glycoprotein overexpressing rats with lithium-pilocarpine-induced chronic temporal lobe epilepsy
Authors: Ziyan Fang, Shuda Chen, Jiaming Qin, Bao Chen, Guanzhong Ni, Ziyi Chen, Jueqian Zhou, Ze Li, Yuping Ning, Chuanbin Wu, Liemin Zhou
Journal: Biomaterials (2016)