tbuckley/cabot-search huggingface dataset:
Prospective randomized study comparing hepatic intra-arterial injection of Yttrium-90 resin-microspheres (HAI-Y90) with protracted IV 5FU (5FU CI) versus 5FU CI alone for patients with liver-limited metastatic colorectal cancer (LMCRC) refractory to standard chemotherapy (CT)
Authors: M. Van Den Eynde, A. Hendlisz, M. Peeters, L. Defreyne, G. Maleux, J. Vannoote, P. Delatte, M. Paesmans, J. Van Laethem, P. Flamen
Journal: Journal of Clinical Oncology (2009)

4096 Background: Chemorefractory LMCRC has a poor prognosis. We hypothesized a significant improvement of the patient's outcome after internal radiotherapy of the hepatic metastases with HAI-Y90 given along with 5FU CI over 5FU CI alone. Methods: This prospective, multicentric, randomized trial compared arm A: 5FU CI (300 mg/m2 D1–14 q3weeks) with arm B: HAI-Y90 and 5FU CI (225 mg/m2 D1–14 followed by 300 mg/m2 D1–14 q3weeks) until disease progression. Eligibility criteria were: chemo-refractory (5FU, oxaliplatin, irinotecan) LMCRC, PS max 2, normal direct bilirubin, and no lung shunting. Primary endpoint was time to liver progression (TTLP). Secondary endpoints were time to progression (TTP), overall survival (OS) and safety. Cross-over (HAI-Y90 monotherapy) was permitted in arm A after disease progression. Analysis was by intention to treat. To detect an increase in median TTLP from 6 to 18 weeks, 35 local progressions were needed (alpha 5%, power 90%). Distribution of time to events variables was modelled through Cox regression (likelihood ratio tests). Results: Trial randomized 46 patients (pts) of whom 44 were eligible for analysis (23 in arm A and 21 in arm B). Pts’ characteristics in the 2 arms were well balanced. Local progression was documented in 41 pts. Median length of follow-up was 108 weeks. Results are summarized in the table . Treatment was well tolerated with few side effects reported, essentially grade 3 asthenia (5 pts; 22%) in arm A. Most pts (25/44) received further treatment after local progression, including 10 pts with cross-over to HAI-Y90 in arm A, which may explain to some degree the lack of difference in OS. Conclusions: HAI-Y90 with 5FU CI significantly improves TTLP and TTP over 5FU CI alone and is a valid salvage therapeutic option for chemo-refractory LMCRC. [Table: see text] No significant financial relationships to disclose.
Audio Interview: Operation Warp Speed and Covid-19
Authors: Eric J. Rubin, Lindsey R. Baden, Stephen Morrissey
Journal: New England Journal of Medicine (2020)

Operation Warp Speed and Covid-19 In this audio interview conducted on August 26, 2020, the editors discuss the U.S. government’s rapid SARS-CoV-2 vaccine development strategy, as well as the recen...
Protective effect of club cell secretory protein (CC-16) on COPD risk and progression: a Mendelian randomisation study
Authors: Stephen Milne, Xuan Li, Ana I Hernandez Cordero, Chen Xi Yang, Michael H Cho, Terri H Beaty, Ingo Ruczinski, Nadia N Hansel, Yohan Bossé, Corry-Anke Brandsma, Don D Sin, Maen Obeidat
Journal: Thorax (2020)

Background The anti-inflammatory pneumoprotein club cell secretory protein-16 (CC-16) is associated with the clinical expression of chronic obstructive pulmonary disease (COPD). We aimed to determine if there is a causal effect of serum CC-16 level on the risk of having COPD and/or its progression using Mendelian randomisation (MR) analysis. Methods We performed a genome-wide association meta-analysis for serum CC-16 in two COPD cohorts (Lung Health Study (LHS), n=3850 and ECLIPSE, n=1702). We then used the CC-16-associated single-nucleotide polymorphisms (SNPs) as instrumental variables in MR analysis to identify a causal effect of serum CC-16 on ‘COPD risk’ (ie, case status in the International COPD Genetics Consortium/UK-Biobank dataset; n=35 735 COPD cases, n=222 076 controls) and ‘COPD progression’ (ie, annual change in forced expiratory volume in 1 s in LHS and ECLIPSE). We also determined the associations between SNPs associated with CC-16 and gene expression using n=1111 lung tissue samples from the Lung Expression Quantitative Trait Locus Study. Results We identified seven SNPs independently associated (p&lt;5×10 –8 ) with serum CC-16 levels; six of these were novel. MR analysis suggested a protective causal effect of increased serum CC-16 on COPD risk (MR estimate (SE) −0.11 (0.04), p=0.008) and progression (LHS only, MR estimate (SE) 7.40 (3.28), p=0.02). Five of the SNPs were also associated with gene expression in lung tissue (at false discovery rate &lt;0.1) of several genes, including the CC-16-encoding gene SCGB1A1 . Conclusion We have identified several novel genetic variants associated with serum CC-16 level in COPD cohorts. These genetic associations suggest a potential causal effect of serum CC-16 on the risk of having COPD and its progression, the biological basis of which warrants further investigation.
Pulsed Field Ablation in Patients With Persistent Atrial Fibrillation
Authors: Vivek Y. Reddy, Ante Anic, Jacob Koruth, Jan Petru, Moritoshi Funasako, Kentaro Minami, Toni Breskovic, Ivan Sikiric, Srinivas R. Dukkipati, Iwanari Kawamura, Petr Neuzil
Journal: Journal of the American College of Cardiology (2020)

Unlike for paroxysmal atrial fibrillation (AF), pulmonary vein isolation (PVI) alone is considered insufficient for many patients with persistent AF. Adjunctive ablation of the left atrial posterior wall (LAPW) may improve outcomes, but is limited by both the difficulty of achieving lesion durability and concerns of damage to the esophagus-situated behind the LAPW.This study sought to assess the safety and lesion durability of pulsed field ablation (PFA) for both PVI and LAPW ablation in persistent AF.PersAFOne is a single-arm study evaluating biphasic, bipolar PFA using a multispline catheter for PVI and LAPW ablation under intracardiac echocardiographic guidance. A focal PFA catheter was used for cavotricuspid isthmus ablation. No esophageal protection strategy was used. Invasive remapping was mandated at 2 to 3 months to assess lesion durability.In 25 patients, acute PVI (96 of 96 pulmonary veins [PVs]; mean ablation time: 22 min; interquartile range [IQR]: 15 to 29 min) and LAPW ablation (24 of 24 patients; median ablation time: 10 min; IQR: 6 to 13 min) were 100% acutely successful with the multispline PFA catheter alone. Using the focal PFA catheter, acute cavotricuspid isthmus block was achieved in 13 of 13 patients (median: 9 min; IQR: 6 to 12 min). The median total procedure time was 125 min (IQR: 108 to 166 min) (including a median of 28 min [IQR: 25 to 33 min] for voltage mapping), with a median of 16 min (IQR: 12 to 23 min) fluoroscopy. Post-procedure esophagogastroduodenoscopy and repeat cardiac computed tomography revealed no mucosal lesions or PV narrowing, respectively. Invasive remapping demonstrated durable isolation (defined by entrance block) in 82 of 85 PVs (96%) and 21 of 21 LAPWs (100%) treated with the pentaspline catheter. In 3 patients, there was localized scar regression of the LAPW ablation, albeit without conduction breakthrough.The unique safety profile of PFA potentiated efficient, safe, and durable PVI and LAPW ablation. This extends the potential role of PFA beyond paroxysmal to persistent forms of AF. (Pulsed Fields for Persistent Atrial Fibrillation [PersAFOne]; NCT04170621).
hTFtarget: A Comprehensive Database for Regulations of Human Transcription Factors and Their Targets
Authors: Qiong Zhang, Wei Liu, Hong-Mei Zhang, Gui-Yan Xie, Ya-Ru Miao, Mengxuan Xia, An-Yuan Guo
Journal: Genomics Proteomics & Bioinformatics (2020)

Transcription factors (TFs) as key regulators play crucial roles in biological processes. The identification of TF-target regulatory relationships is a key step for revealing functions of TFs and their regulations on gene expression. The accumulated data of chromatin immunoprecipitation sequencing (ChIP-seq) provide great opportunities to discover the TF-target regulations across different conditions. In this study, we constructed a database named hTFtarget, which integrated huge human TF target resources (7190 ChIP-seq samples of 659 TFs and high-confidence binding sites of 699 TFs) and epigenetic modification information to predict accurate TF-target regulations. hTFtarget offers the following functions for users to explore TF-target regulations: (1) browse or search general targets of a query TF across datasets; (2) browse TF-target regulations for a query TF in a specific dataset or tissue; (3) search potential TFs for a given target gene or non-coding RNA; (4) investigate co-association between TFs in cell lines; (5) explore potential co-regulations for given target genes or TFs; (6) predict candidate TF binding sites on given DNA sequences; (7) visualize ChIP-seq peaks for different TFs and conditions in a genome browser. hTFtarget provides a comprehensive, reliable and user-friendly resource for exploring human TF-target regulations, which will be very useful for a wide range of users in the TF and gene expression regulation community. hTFtarget is available at http://bioinfo.life.hust.edu.cn/hTFtarget.
Comparability of health-related quality of life (HRQOL), treatment decision making, and treatment satisfaction after PSA recurrence among prostate cancer patients who receive hormone therapy (HT) versus observation (OBS): Results from the COMPARE registry
Authors: T. Luu, O. Sartor, N. Dandade, S. Halabi, C. Bennett
Journal: Journal of Clinical Oncology (2009)

5131 Background: HT may lower PSA, but it may also cause hot flashes and sexual dysfunction. OBS is not associated with hot flashes or lower testosterone production, but PSA may rise. Examining patient satisfaction with treatment decision making, treatment choice, and HRQOL may help improve disease management. We compared treatment satisfaction and HRQOL of patients who chose OBS over HT. Methods: The Comprehensive Multicenter Prostate Adenocarcinoma Registry (COMPARE) is an observational registry of men with PSA failure. Data from patient-reported questionnaires were analyzed for patients treated with OBS or HT. Results: 674 patients (82%) chose OBS; 147 (18%) chose HT. The median time between cancer diagnosis and registry enrollment was 6 years. Of men on OBS, 85%, 83%, and 71% were satisfied with treatment decision process, treatment choice, and treatment outcome, respectively. Men on HT had similar rates of satisfaction (82%, 75%, and 71%). Men initially treated with brachytherapy/surgery were less satisfied with OBS. Men initially treated with external beam radiation were less satisfied with HT. Patients reported similar problems with urinary, sexual, and bowel function. Conclusions: Men with PSA failure seem content with treatment choice and decision making and have low rates of urinary/bowel problems. Rates of sexual dysfunction in both groups are similar. Clinical trials may help determine if HT improves long-term outcomes (e.g. overall survival), since short-term patient reported satisfaction is similar between OBS and HT. The reported rate of sexual dysfunction is lower than expected. [Table: see text] [Table: see text]
Abstract 6462: Radiomics features of 18F-fluorodeoxyglucose positron-emission tomography as a novel prognostic signature in colorectal cancer
Authors: Jeonghyun Kang, Jean Rene Clemenceau, Sunho Park, Hongming Xu, Changjin Hong, Tae Hyun Hwang
Journal: Cancer Research (2020)

Abstract Background: The aim of this study was to investigate the prognostic value of radiomics signatures derived from 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET) in patients with colorectal cancer (CRC). Methods: This was a retrospective, single-center study. From April 2008 to Jan 2014, we identified CRC patients who underwent 18F-FDG-PET before starting any neoadjuvant treatments and surgery. Radiomics features were extracted from the primary lesions identified on 18F-FDG-PET. Patients were divided into a training and a validation set by random sampling. A least absolute shrinkage and selection operator (LASSO) Cox regression model was applied for prognostic signature building with progression-free survival (PFS) using the training data set. Using the calculated radiomics score, a nomogram was developed, and the clinical utility of this nomogram was assessed in the validation set. Results: Three-hundred-and-eight-one patients with surgically resected CRC patients (training set 228 vs. validation set 153) were included. In the training set, a radiomics signature called a rad_score was generated using two PET-derived features such as Gray Level Run Length Matrix_Long-Run Emphasis (GLRLM_LRE) and Grey-Level Zone Length Matrix_Short-Zone Low Gray-level Emphasis (GLZLM_SZLGE). Patients with a high-rad_score in the training and the validation set had shorter PFS (P &amp;lt; 0.001 in the training set and P = 0.008 in the validation set). In the multivariable analysis with forward selection, presence of lymphovascular invasion (LVI) (hazard ratio [HR] 3.73; 95% confidence interval [CI], 1.63-8.47; P = 0.001), pathological node-positivity (HR 2.52; 95% CI, 1.01-6.26; P = 0.046), and a high rad_score (HR 7.82; 95% CI, 2.36-25.85; P &amp;lt; 0.001) remained independent predictors of a worse prognosis in the training set. The rad_score was also identified as an independent prognostic factor in the validation and the overall set. A radiomics nomogram was developed using the rad_score, pathological node stage, and lymphovascular invasion, and showed good performance in the calibration curve in the validation set. Conclusions: Textural features, such as GLRLM_LRE and GLZLM_SZLGE, derived from 18F-FDG-PET images may enable more detailed stratification of prognosis in patients with CRC. Citation Format: Jeonghyun Kang, Jean Rene Clemenceau, Sunho Park, Hongming Xu, Changjin Hong, Tae Hyun Hwang. Radiomics features of 18F-fluorodeoxyglucose positron-emission tomography as a novel prognostic signature in colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6462.
The effect of toremifene citrate on BMD in men on ADT: A phase III clinical trial
Authors: K. A. Veverka, B. Malkowicz, M. Smith, R. A. Morton, M. S. Steiner
Journal: Journal of Clinical Oncology (2009)

5055 Background: Androgen deprivation therapy decreases bone mineral density and increases fracture incidence. In a recently completed two-year randomized controlled trial of 1382 men, toremifene increased BMD and decreased vertebral fracture incidence in men receiving ADT for prostate cancer. We now describe the effects of toremifene on BMD in various subject subgroups. Methods: We conducted a randomized double blind placebo controlled trial in 1382 men with histologically confirmed prostate cancer on ADT. Key entry criteria included age ≥ 50 years, continuous ADT for 6 months or longer or intermittent ADT for 12 months or longer. Subjects on intermittent ADT at enrollment had to remain on continuous ADT for the duration of their time on study. Subjects were randomized to receive either 80mg toremifene citrate daily or matching placebo. The primary end point was the incidence of new morphometric vertebral fractures. Secondary endpoints included BMD, clinical fragility fractures, bone turnover markers, lipid profile, hot flashes, and gynecomastia. Results: In the overall study population, toremifene increase BMD of the hip and lumbar spine by 1.6% and 2% after two years compared to placebo. Similar beneficial effects of toremifene were observed in each of the subgroups ( Table ). Conclusions: Toremifene significantly increases bone mineral density of the hip and spine in every subgroup including those men who were older or had prevalent vertebral fractures, longer exposure to ADT, or lower baseline BMD. [Table: see text] [Table: see text]
Utilization of Internet-based survivorship care plans by survivors of gynecologic cancers
Authors: C. E. Hill-Kayser, C. Vachani, M. K. Hampshire, L. A. Jacobs, J. M. Metz
Journal: Journal of Clinical Oncology (2009)

5592 Background: Survivors of gynecologic cancers may be at risk for cancer-related late-effects, including fatigue, pain, second malignancy risk, and sexual side effects. The Institute of Medicine has recommended survivorship care plans (SCP) for all cancer survivors. Methods: A program for creation of SCP, OncoLife, is publicly accessible through OncoLink ( www.oncolink.org ), serving over 3.9 million pages/month to 385,000 unique IP addresses (August 2008). Users responding to 17 queries regarding demographics, diagnosis, and treatment receive comprehensive, individualized guidelines for future care. User data is maintained anonymously and securely, with IRB approval. Results: From May 2007-November 2008, 3,343 individuals completed OncoLife surveys. Survivors of gynecologic cancers represented 8% (n = 272; 58% ovarian, 24% endometrial, 19% cervical). Median ages at diagnosis of ovarian, endometrial, and cervical cancer were 50, 51, and 35 yrs, respectively, and median current ages 53, 55, and 47. Surgery was undergone by 98% of ovarian, 97% of endometrial, and 81% of cervical cancer survivors, and chemotherapy/ radiotherapy by 91%/12%, 51%/59%, and 67%/67%, respectively. Known genetic syndromes were reported by 13% of ovarian cancer survivors, compared to &lt; 1% of endometrial/ cervix cancer survivors (p = 0.0006). Of all gynecologic cancer survivors, 53% reported being followed by an oncologist, 14% a primary care provider (PCP), and 27% both. Only 7% had received survivorship information previously. Conclusions: Most survivors of gynecologic malignancies have undergone multimodality treatment and may particularly benefit from SCP guidelines. Most do not receive follow-up care from both an oncologist and PCP, and few have received survivorship information. Gynecologic cancer survivors appear willing to use this tool; future iterations will focus on further individualization of guidelines, and improving access to underrepresented populations. No significant financial relationships to disclose.
Functional respiratory imaging identifies redistribution of pulmonary blood flow in patients with COVID-19
Authors: Muhunthan Thillai, Chinmay Patvardhan, Emilia M Swietlik, Tom McLellan, Jan De Backer, Maarten Lanclus, Wilfried De Backer, Alessandro Ruggiero
Journal: Thorax (2020)

An increasing observation is that some patients with COVID-19 have normal lung compliance but significant hypoxaemia different from typical acute respiratory distress syndrome (ARDS). We hypothesised that changes in pulmonary blood distribution may be partially responsible and used functional respiratory imaging on CT scans to calculate pulmonary blood volume. We found that patients with COVID-19 had significantly reduced blood volume in the smaller calibre blood vessels (here defined as &lt;5 mm 2 cross-sectional area) compared with matched ARDS patients and healthy controls. This suggests that using high levels of PEEP may not alone be enough to oxygenate these patients and that additional management strategies may be needed.
Publisher Correction: Keap1 mutation renders lung adenocarcinomas dependent on Slc33a1
Authors: Rodrigo Romero, Francisco J. Sánchez-Rivera, Peter M. K. Westcott, Kim L. Mercer, Arjun Bhutkar, Alexander Muir, Tania J. González Robles, Swanny Lamboy Rodríguez, Laura Z. Liao, Sheng Rong Ng, Leanne Li, Caterina I. Colón, Santiago Naranjo, Mary Clare Beytagh, Caroline A. Lewis, Peggy P. Hsu, Roderick T. Bronson, Matthew G. Vander Heiden, Tyler Jacks
Journal: Nature Cancer (2020)
SAT0099 Soft tissue rheumatism in iraqi diabetic patients
Authors: TA Samad
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> MB ChB, DMR(RCP) London. Consultant Rheumatologist for the last 20 years in Baghadad Medical City (a teaching hospital). Ass. Prof. in Baghdad University-College of Medicine. <h3>Objectives</h3> To study the prevalence of soft tissue rheumatism in Iraqi diabetic patients (both IDDM and NIDDM) and to evaluate association between these sequelae and the duration of the diease. <h3>Methods</h3> Limited joint mobility (LJM), Dupuytren’s Contracture (DC), flexor tenosynovitis (FTS), frozen shoulder (FS) and carpal tunnel syndrome (CTS) were assessed in 100 Iraqi diabetics (50 insulin dependent, 50 non insulin dependent DM) and (50) nondiabetic control matched for age and sex, according to clinical examination (signs and symptoms) and electrophysiological study. <h3>Results</h3> Prevalence of LJM, in IDDM vs. NIDDM was (56% vs. 36%), FTS (20% vs. 38%), DC(20% vs 16%), FS(22% vs 40%) and CTS(26% vs 16%). There was significant statistical difference (p &lt; 0.05) between IDDM and NIDDM, regarding LJM, FS, and FTS, the first was higher in IDDM and the last two were higer in NIDDM, while there was no significant and statistical difference regarding CTS and DC. <h3>Conclusion</h3> Soft tissue Rheumatism occurs more frequently in both IDDM and NIDDM than in control (p &lt; 0.05). Their occurrence appeared to be directly related to disease duration regarding LJM, DC and CTS. The most common sequelae in IDDM was LJM while FS was the most frequent abnormality detected in NIDDM. Patients with IDDM had been found to be more susceptible to develop multiple rheumatic sequelae than patients with NIDDM(p &lt; 0.05).
Effect of proton pump inhibitor co-medication on imatinib disposition: A healthy volunteer study
Authors: J. H. Beumer, D. D. Shah, M. Yerk, K. A. Komazec, S. Christner, L. J. Appleman, R. R. Redner, B. M. Miller, M. J. Egorin
Journal: Journal of Clinical Oncology (2009)

2503 Background: Imatinib mesylate, a potent inhibitor of Bcr-Abl and c-kit tyrosine kinases, is widely used to treat gastrointestinal stromal tumors and Philadelphia chromosome-positive leukemias. Imatinib often causes gastric upset and is therefore frequently administered with a proton pump inhibitor (PPI). Yet, the resulting elevated gastric pH, delayed gastric emptying, and inhibition of ABC transporters in the gut could change imatinib absorption, thereby affecting the therapeutic effectiveness of imatinib. To test this hypothesis, we sought to define the effect of PPI on the plasma pharmacokinetics of imatinib. Methods: 11 healthy subjects (6 M, 5 F; 21–56 years) were enrolled in a 2-period, open-label, randomized cross-over, fixed- sequence study. In one period, they received a single 400 mg dose of imatinib p.o., in the other, 40 mg omeprazol daily for five days followed by a single 400 mg dose of imatinib p.o.. The periods were separated by a wash-out period of ≥ 14 days. Plasma samples from 0–72 h after dosing were obtained. Plasma concentrations of imatinib and its active metabolite CGP74588 were determined with an LC-MS assay and data were analyzed non-compartmentally. The study was powered to detect a 30% difference in imatinib AUC with 80% power and a 5% type I error. Results: See Table . Conclusions: This study demonstrates that the use of PPI to treat imatinib-induced gastric upset does not significantly affect imatinib plasma AUC. Support: Novartis; NIH/NCRR/CTSA Grant UL1 RR024153 [Table: see text] [Table: see text]