tbuckley/cabot-search huggingface dataset:
Biological Associations and Clinical Impact of Differential Expression of the Pre-Mir-29a/b-1 and Pre-Mir-29b-2/C Clusters in Acute Myeloid Leukemia
Authors: Florian Ramdohr, Marius Bill, Madlen Jentzsch, Karoline Schubert, Juliane Grimm, Julia Schulz, Luba Schuhmann, Laura Katharina Schmalbrock, Lynn Baquiran Bonifacio, Stefanie Beinicke, Janine Haentschel, Wolfram Poenisch, Vladan Vucinic, Georg-Nikolaus Franke, Thoralf Lange, Michael Cross, Gerhard Behre, Dietger Niederwieser, Sebastian Schwind
Journal: Blood (2016)
Young people, alcohol, and designer drinks
Authors: P. Catterson, S. Hilton, M. White, A. M. MacKintosh, G. Hastings, K. Hughes, C. Wheeler, J. Watson, J. Inglis
Journal: BMJ (1997)

Reports of an apparent decline in the incidence of neural tube defects (NTDs) have come from various parts of the world. If these findings are consistent they would have an important impact on prenatal diagnosis and on screening programs. The incidence of NTDs over a 10-year period was examined in British Columbia, a province that has a population-based health surveillance registry through which there is virtually complete ascertainment of liveborn infants with NTDs. The results showed a significant decrease in incidence only for stillborn infants with anencephaly. The increased use of ultrasonography and the subsequent termination of pregnancies in which the fetus has been found to have anencephaly may explain this observation.
Effectiveness of HDU in the immediate post operative management of two-stage oesophagectomy patients
Authors: BR Gopinath, PC Munipalle, PP Vassallo, U Contractor, PA Davis, YKS Viswanath
Journal: Endoscopy (2006)

Aims: To assess logistics and cost effectiveness of primary HDU care in the immediate post operative period up to day 5 following two-stage oesophagectomy (TSO) in a tertiary referral centre.
Complete response of advanced hepatocellular carcinoma to sorafenib : another case and a comprehensive review
Authors: Tae Suk Kim, Ji Hoon Kim, Baek hui Kim, Young-Sun Lee, Yang Jae Yoo, Seong Hee Kang, Sang-June Suh, Young Kul Jung, Yeon Seok Seo, Hyung Joon Yim, Jong Eun Yeon, Kwan Soo Byun
Journal: Clinical and Molecular Hepatology (2017)

Since sorafenib was introduced in 2007 for treating advanced hepatocellular carcinoma (HCC), 15 patients have achieved a complete response (CR) in advanced HCC. However, only four of these reports can be regarded as real CRs involving adequate assessments including imaging, serum tumor markers, and histologic examinations of completely resected specimens. A 54-year-old man with hepatitis C virus (HCV)-related liver cirrhosis (LC) presented to our unit. A CT scan demonstrated a 3.8-cm arterial hypervascular/portal-washout mass in the right lobe and invasion in the right portal vein. Twelve weeks after beginning sorafenib therapy, the AFP level was normalized and a CT scan showed a prominent decrease in the hepatic mass and a significant decrease in the volume of portal vein thrombosis (PVT). The patient received a right liver hemihepatectomy after 12 months. No viable tumor cells were found in the resected specimen, and there was no thrombotic obstruction of the portal vein. Twelve months later the patient showed no clinical evidence of HCC recurrence. This is the first case of CR in HCC treatment following sorafenib with histologically confirmed HCV-related HCC without LC evidence, HCC with PVT, and a follow-up of longer than 12 months. This case seems to be an extremely unusual clinical outcome in advanced HCC.
Impact de l'échoendoscopie dans le diagnostic des pancréatites aiguës «idiopathiques»: étude prospective trois ans après la conférence de consensus
Authors: P Andrau, B Bournet, P Faure, J Moreau, J Frexinos, J Escourrou, L Buscail
Journal: Endoscopy (2005)

Au cours de la conférence de consensus de 2001, l'échoendoscopie (EE) était considérée comme un des meilleurs examens complémentaires pour le diagnostic étiologique des pancréatites aiguës (PA) non-alcooliques et non-biliaires, des PA biliaires ou des PA classées initialement idiopathiques (PAI). Le but de cette étude était d'évaluer de façon prospective, à partir du recrutement d'un centre référent régional, l'impact réel de la pratique de l'échoendoscopie réalisée à distance d'une PAI selon les recommandations de la conférence de consensus 2001.
Similar decrease of proliferation employing Ki-67 after brief neoadjuvant hormonal treatment on luminal A versus luminal B estrogen receptor positive breast cancer patients.
Authors: Tu Quach, Randell Skau, Elizabeth Johnston, Rebecca Vierra, Tien Nguyen, John Promlap, Milton Conley, Ravi Nagubandi, Edward J. Ordorica, Susan Schmidt, Lucie Tomanova, Steve DeMartini, Greg Schneringer, Leona Roberts, Ashley Schaffer, Martin Majer, Megan Powell
Journal: Journal of Clinical Oncology (2016)

e12020 Background: Complete pathological responses after neoadjuvant chemotherapy predict disease-free survival and overall survival but they are rare following neoadjuvant endocrine therapy. Significant decrease in proliferation rate after short hormonal therapy estimated by Ki-67 marker became predictor and surrogate of later clinical response in clinical trials. Numerous studies have shown a relationship between Ki-67 status and early breast cancer biology. High Ki-67 levels in estrogen receptor positive (ER+) breast cancer are often associated with luminal B breast cancer which has higher risk of relapse and worse breast cancer survival. An exact cut-off point to differentiate between Luminal A and Luminal B using Ki-67 has changed recently. Methods: This retrospective observational study was performed in a single institution serving rural indigenous community at Oroville Hospital in Oroville, California. Data was collected over five years (2011 to 2016) from 56 estrogen-positive breast cancer patients with ages ranging from 46 to 87 years (mean 69 years). The majority of patients (52 of 56) had either stage 1 or 2 cancer and the rest of patients (4 of 56) had stage 4 breast cancer. Ki-67 was measured prior to treatment then measured once more at least 2 weeks on treatment. Patients were treated with either Tamoxifen (5 out of 56) or aromatase inhibitor (AI) (51 out of 56) prior to surgical removal by lumpectomy/mastectomy. Positive response was set as a 50% reduction in Ki-67. Response rates were compared with a chi-squared test using three common Ki-67 cut off points (12%, 15%, 20%) to determine if there is a difference in endocrine therapy effect based on Luminal subtype. Results: Chi-square analysis found no statistically significant difference between response rate ratios at all Ki-67 cut off points (p = 0.63 for 20%, p = 0.77 for 15%, and p = 0.77 for 12%). Conclusions: When using endocrine therapy, there is no observable statistical difference in response rates between Luminal A and Luminal B breast cancer patients.
Reviews and Meta-analyses of Psychotherapy Efficacy for Borderline Personality Disorder
Authors: Erlend Glasø Faltinsen, Mickey Kongerslev, Ole Jakob Storebø
Journal: JAMA Psychiatry (2017)

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Survival outcomes after adjuvant radiation in women ≥ 65 years diagnosed with ductal carcinoma in-situ: Analysis of National Cancer Data Base.
Authors: Wenli Gao, Prakash Peddi, Gary Von Burton, Runhua Shi
Journal: Journal of Clinical Oncology (2016)

1058 Background: Adjuvant radiation (XRT) following breast conservative therapy (BCT) is an established clinical guideline in patients diagnosed with ductal carcinoma in situ (DCIS). We analyzed survival outcomes in women ≥ 65 years undergoing adjuvant XRT after partial mastectomy using the National Cancer Data Base (NCDB). Methods: We reviewed a cohort of 10,912 female patients ≥ 65 years, with DCIS diagnosed between 2004 and 2012 registered in the NCDB. The impact of adjuvant XRT following surgical resection on overall survival was analyzed. Patient demographics, co-morbidities and tumor characteristics were also analyzed for survival impact. Univariate and multivariate analysis was performed. Results: A total of 10,912 patients ≥ 65 years were analyzed. 54% were below 75 years and 46% were above 75 years. Caucasians comprised 87%, African Americans 11% and Asians 2%. A total of 11.48% underwent partial mastectomy (PM) only, 39.54% underwent total mastectomy (TM) only, 19.21% PM and XRT, 3.03% PM and anti-hormonal therapy (HT), 16.86 % PM plus XRT and HT, 9.34% TM and HT. Multivariate analysis demonstrated that advanced age, higher comorbidities, lower income levels, and increased tumor size were significant predictors of death. Multivariate analysis showed that the addition of adjuvant XRT in patients with PM or in patients with PM+HT did not decrease the risk of death. Hazard Ratios compared to PM alone were as follows: 1) PM+HT: 0.76 (95% CI 0.44-1.33), 2) PM+XRT: 3.81 (95% CI 0.51-28.19) and 3) PM+HT+XRT: 2.91 (95% CI 0.39-25.91). Conclusions: Our analysis demonstrates that the addition of adjuvant radiation in women ≥ 65 years diagnosed with DCIS undergoing BCT may not improve overall survival. The potential benefit of XRT in preventing loco-regional recurrence could not be analyzed from the NCDB.
SGN-CD48A: a Novel Humanized Anti-CD48 Antibody-Drug Conjugate for the Treatment of Multiple Myeloma
Authors: Tim S. Lewis, Devra Olson, Kristine Gordon, Sharsti Sandall, Marsha Quick, Margo Finn, Lori Westendorf, Germein Linares, Chris Leiske, Albina Nesterova, Lanshan Huang, Maitrayee Goswami, Sa Wang, Che-Leung Law
Journal: Blood (2016)
Comparative efficacy with endocrine-based combination versus monotherapy among postmenopausal women with HR+/ HER2- metastatic breast cancer: A network meta-analysis.
Authors: Derek Tang, Rajeev Ayyagari, Oscar Patterson-Lomba, Zhou Zhou, Jipan Xie, Polly Ann Niravath
Journal: Journal of Clinical Oncology (2017)

e12535 Background: Endocrine-based therapies (ETs) are used to treat postmenopausal women with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) advanced breast cancer (ABC). This study synthesizes the available evidence on progression-free survival (PFS), overall response rate (ORR) and clinical benefit rate (CBR) with ETs, as monotherapy and in combination with targeted therapy (TT), in postmenopausal HR+/HER2- ABC using a mixed treatment comparison (MTC). Methods: A systematic literature review of Medline, EMBASE, Cochrane Library and key conferences (2013-2016) was performed to identify randomized clinical trials satisfying the following criteria: 1) included women with HR+/HER2- ABC, 2) included ET monotherapy and ET+TT combination arms, 3) reported PFS, ORR or CBR, and 4) was published in 2007 or later (when HER2 testing was standardized). Pairwise hazard ratios (HRs), relative risks (RR) and their corresponding 95% credible intervals (CrIs) were obtained via a Bayesian MTC. Efficacy was studied in first-line and aromatase inhibitor (AI)-failure (included patients who previously failed an AI or chemotherapy as first-line therapy) settings separately. ETs included letrozole, fulvestrant and exemestane, while ribociclib, palbociclib and everolimus were the TTs identified. Results: Three trials were eligible in the first setting for all three outcomes. TT+ET had significantly longer PFS vs. ET (HR = 0.56, 95% CrI 0.48-0.65), and also had significantly higher ORR (RR = 1.34, 1.17-1.51) and CBR vs. ET (RR = 1.17, 1.12-1.23). In the AI-failure setting, three trials were eligible for PFS, two for ORR, and none for CBR. TT+ET significantly improved PFS vs. ET (HR = 0.47, 0.41-0.53) and had significantly higher ORR vs. ET (RR = 3.52, 2.26-5.39). Conclusions: These results consistently indicate that the hazard of progression or death was approximately halved and that overall response and clinical benefit rates were significantly improved across patient settings for patients receiving TT+ET relative to ET monotherapy among postmenopausal women with HR+/HER2- ABC women.
A multi-centre study to investigate the natural history of taxane acute pain syndrome (TAPS) in patients receiving taxane-based chemotherapy for breast or prostate cancer.
Authors: Ricardo Fernandes, Sasha Mazzarello, Mohammed FK Ibrahim, John Frederick Hilton, Anil Abraham Joy, Michael Ong, Brian Hutton, Lisa Vandermeer, Mark J. Clemons
Journal: Journal of Clinical Oncology (2016)

e21594 Background: Taxane acute pain syndrome (TAPS) is characterized by myalgia and arthralgia starting 24-48 hours after receiving taxane-based chemotherapy and lasting up to 7 days. Despite its negative impact on patient quality of life (QoL), its characteristics and natural history remain poorly defined. The present study evaluates persistence, severity and the impact of TAPS on QoL. Methods: Breast or prostate cancers patients commencing taxane-based chemotherapy completed the Functional Assessment of Cancer Therapy-Taxane (FACT-T), Brief Pain Inventory (BPI) questionnaires and a pain medication diary every day for 1 week after each chemotherapy infusion. Results: From March to December 2015, of 52 patients enrolled, 25 (breast n=21, prostate n=4) completed the study. TAPS started 24-72 hours (range 24-96) after infusion reaching a peak by day 3 (range 1-5), and was more often reported in the legs and back. Table 1 shows the TAPS characteristics. There were no dose reductions, delays or treatment discontinuation required due to TAPS. Medications used to treat TAPS included opioids (n=5) and NSAIDs (n=9). There was a negative effect of pain on QoL in both scores at baseline in comparison with the final infusion administered (mean change in “BPI worst pain” score was +1.61(p=0.014) and FACT-T score was -6.9 (p=0.017). Study expected to be completed by April 2016. Conclusions: TAPS is a common toxicity associated with a negative impact on QoL. Further data will help define predisposing risk factors. Prospective patient-reported outcome assessments are crucial to help individualize treatment strategies and improve management of TAPS. Clinical trial information: NCT02362087.TAPS characteristics. TC (n=10) FEC-D (n=2) Single T (N=9) AC-P or AC-D (n=3) TAPS Incidence 80% 50% 22% 100% TAPS Duration (days) (median, mean) 1 – 5 (4, 3.26) 2– 4 (3,3) 2 – 5 (3, 3.4) 3 – 5 (4, 3.72) Growth factor use (n) 7 1 0 1 Taxane Dosing at 100 mg/m2 No Yes No Yes Oral Steroids use (n) 8 1 0 2 TC – cyclophosphamide-docetaxel; FEC-D- 5-fluorouracil-epirrubicin-cyclophosphamide + docetaxel; Single T- paclitaxel ; AC-D - doxorubicin- cyclophosphamide + docetaxel; AC-T - doxorubicin-cyclophosphamide + paclitaxel
The rhetoric of research
Authors: A J Singleton
Journal: BMJ (1995)

referrals may well have reversed since 1991 because of the NHS reforms, which have seen so many radical changes in both general practice and the hospital sector.Until more up to date national data are available, Armstrong and Nicoll's argument, which is based on historical trends, may not be applicable.In addition, our figures show a small decrease in the number of patients followed up during the period.This is contrary to Armstrong and Nicoll's suggestion that the problem of recycling patients has become worse in recent years and has resulted in access for new outpatient referrals being blocked.
Epidemiology and survival trends of epithelial ovarian cancer (EOC) subtypes in SEER database: Time to focus on minor histologies.
Authors: Samuel Guan Wei Ow, Hua-Ling Tsai, Norma Kanarek
Journal: Journal of Clinical Oncology (2016)

1561 Background: Management of EOC is largely based on the more common serous (SC) and endometroid (EnC) subtypes, but differences in clinical characteristics of less common histologies such as clear cell (CC), mucinous (MC) and malignant mixed mullerian tumor (MMMT) are increasingly clear. Yet, treatment strategies remain uniform. Methods: We obtained data on incident EOC cases from the Surveillance, Epidemiology and End Results (SEER 13) database between 1993-2007, and compared their disease characteristics. Survival analysis was performed using Kaplan-Meier and flexible parametric models. Results: Of 25358 incident EOC cases, 15405 (60.8%) had SC, 2748 (10.8%) EnC, 4264 (16.8%) MC, 1913 (7.5%) CC and 1028 (4.1%) MMMT. Age adjusted incidence rate per 100K (standard US 2000 population) was highest in SC (5.3), followed by EnC (1.5), MC (1.0), CC (0.7) and MMMT (0.4). The proportion of CC, MC and MMMT was more common in Asians (15.1%), American Indians (15.4%) and Blacks (5.4%) respectively (p<0.001). Mean age of onset was earlier in CC (56.3y), EnC (56.6) and MC (56.7) vs SC (62.4) and MMMT (66.1) (p<0.001). Lymph node involvement was more likely in SC (22.1%) compared to MMMT (14.7%), CC (10.3%), EnC (7.8%) and MC (4.9%) (p<0.001). Advanced stage (FIGO 3 / 4) was more common in SC (77.5%) & MMMT (68.5%) vs CC (28%), EnC (31%) & MC (35.2%) (p<0.001). Across stages, 5y EOC-specific survival was worst in MMMT, while EnC fared the best (p<0.001). Comparing trends across 1993-97, 1998-2002 and 2003-07, stage-adjusted EOC-specific survival improved with time (HR 0.90, p<0.001). However, this improvement was limited to EnC (HR 0.74) and SC (HR 0.89) (p<0.001), but not in CC (HR 0.84), MMMT (HR 1.05) and MC (HR 1.14) (p>0.05), suggesting that the conventional one-size-fits-all treatment approach may not be appropriate. Conclusions: The disparate clinical characteristics and inferior prognosis of minor EOC subtypes are evident in this large population cancer registry study, and underpins the importance of managing CC, MC and MMMT as separate disease entities with individualized therapies. 5y EOC-specific survival (%). FIGO SC EnC CC MC MMMT 1 86.2 94.2 85.5 92.2 72.1 2 70.2 82.9 66.7 65.0 47.8 3 37.8 53.5 26.9 35.5 24.5 4 24.9 35.3 17.0 19.3 15.6
Erratum: Pretransplant minimal residual disease level predicts clinical outcome in patients with acute myeloid leukemia receiving high-dose chemotherapy and autologous stem cell transplantation
Authors: A Venditti, L Maurillo, F Buccisano, G Del Poeta, C Mazzone, A Tamburini, M I Del Principe, M I Consalvo, P De Fabritiis, L Cudillo, A Picardi, A Franchi, F L Coco, S Amadori
Journal: Leukemia (2004)
Abstract 343: Bayesian Selection of Modifier Genes in Hypertrophic Cardiomyopathy Through Whole Genome Sequencing
Authors: Matthew Wheeler, Daryl Waggott, Megan Grove, Frederick Dewey, Cuiping Pan, Aleks Pavlovic, Rachel Goldfeder, Megan Puckelwartz, Sharlene Day, Elizabeth McNally, Gerald W Dorn, Euan Ashley
Journal: Circulation Research (2015)

Background: Technological advances have greatly reduced the cost of whole genome sequencing. For single individuals clinical application is apparent, while exome sequencing in tens of thousands of people has allowed a more global view of genetic variation that can inform interpretation of specific variants in individuals. We hypothesized that genome sequencing of patients with monogenic cardiomyopathy would facilitate discovery of genetic modifiers of phenotype. Methods and Results: We identified 48 individuals diagnosed with cardiomyopathy and with putative mutations in MYH7, the gene encoding beta myosin heavy chain. We carried out whole genome sequencing and applied a newly developed analytical pipeline optimized for discovery of genes modifying severity of clinical presentation and outcomes. Using a combination of external priors and rare variant burden tests we scored genes as potential modifiers. There were 96 genes that reached a modifier score of 6 out of 12 or better (9=2, 8=8, 7=17, 6=69). We identified NCKAP1, a gene that regulates actin filament dynamics, and CAMSAP1, a calmodulin regulate gene that regulates microtubule dynamics, as top scoring modifiers of hypertrophic cardiomyopathy phenotypes (score=9) while LDB2, RYR2, FBN1 and ATP1A2 had modifier scores of 8. Of the top scoring genes, 21 out of 96 were identified as candidates a priori. Our candidate prioritization scheme identified the previously described modifiers of cardiomyopathy phenotype, FHOD3 and MYBPC3, as top scoring genes. We identified structural variants in 21 clinically sequenced cardiomyopathy associated genes, 13 of which were at less than 10% frequency. Copy number variants in ILK and CSRP3 were nominally associated with ejection fraction (p=0.03), while 8 genes showed copy gains (GLA, FKTN, SGCD, TTN, SOS1, ANKRD1, VCL and NEBL). Structural variants were found in CSRP3, MYL3 and TNNC1, all of which have been implicated as causative for HCM. Conclusion: Evaluation of the whole genome sequence, even in the case of putatively monogenic disease, leads to important diagnostic and scientific insights not revealed by panel-based sequencing.
Structural Insights into Modulation of Neurexin-Neuroligin Trans -synaptic Adhesion by MDGA1/Neuroligin-2 Complex
Authors: Jung A Kim, Doyoun Kim, Seoung Youn Won, Kyung Ah Han, Dongseok Park, Eunju Cho, Nayoung Yun, Hyun Joo An, Ji Won Um, Eunjoon Kim, Jie-Oh Lee, Jaewon Ko, Ho Min Kim
Journal: Neuron (2017)
Abstract 16042: Echocardiography Ramp Test in Continuous-Flow Left Ventricular Assist Devices and Aortic Regurgitation: Do Loading Conditions Matter?
Authors: Sirtaz Adatya, Peter Eckman, Monica M Colvin-Adams, S. C Masri
Journal: Circulation (2013)

INTRODUCTION:  An echocardiographic ramp speed test (RST) is a novel approach to evaluate suspected device obstruction after continuous-flow left ventricular assist device (CF-LVAD) implant. Failure to reduce the left ventricular end diastolic dimension (LVEDD) with increasing CF-LVAD speeds has been shown to be highly predictive of pump obstruction. However, the presence of aortic regurgitation (AI) in patients with CF-LVAD imposes an increase on loading conditions that could alter the predictive power of RST.   Hypotheses:  In the presence of at least mild to moderate AI and no evidence of device obstruction, the LVEDD-speed slope is abnormal.   Methods and Results:  Ten RSTs were prospectively performed in patients with at least mild to moderate continuous AI (Group I) without clinical suspicion of obstruction and were compared to eighteen patients on CF- LVAD support with no or mild AI and no suspicion of obstruction (Group II). Echocardiography was performed to assess severity of AI and LVEDD. The results of the speed versus LVEDD, pulsatility index (PI) and power (PW) were plotted and linear function slopes were calculated. Eighty percent of the patients with at least mild to moderate AI had a flat LVEDD/speed slope > -0.16. In comparison, all the patients in Group II had a normal LVEDD/speed slope.   CONCLUSION:  RST is a useful diagnostic tool for diagnosing CF-LVAD device obstruction, but in the presence of at least mild to moderate AI, increasing pump speed does not lead to effective decompression of the left ventricle and results in an abnormal slope LVEDD/speed slope. Longitudinal studies are needed to clarify the diagnostic role of RST in the setting of increased loading conditions
An IGF2BP3-Cdk9 Pathway Governs the Human Fetal-Adult Megakaryocyte Transition
Authors: Kamaleldin E Elagib, Chih-Huan Lu, Goar Mosoyan, Ewelina Zasadzińska, Daniel R Foltz, Peter Balogh, Els Verhoeyen, Miriam Sansó, Robert P Fisher, Camelia Iancu-Rubin, Adam N Goldfarb
Journal: Blood (2016)