tbuckley/cabot-search huggingface dataset:
Targeting transcription-coupled nucleotide excision repair overcomes resistance in chronic lymphocytic leukemia
Authors: G Lohmann, E Vasyutina, J Bloehdorn, N Reinart, J I Schneider, V Babu, G Knittel, G Crispatzu, P Mayer, C Prinz, J K Muenzner, B Biersack, D G Efremov, L Chessa, C D Herling, S Stilgenbauer, M Hallek, R Schobert, H C Reinhardt, B Schumacher, M Herling
Journal: Leukemia (2016)
Characterization of the Proteomic and Genomic Profiles of Chronic Lymphocytic Leukemia Patients with Distinct Clinical Prognosis According to the Mutational Status of the IgVH and BCL6 and Expression Level of CD38 and ZAP70.
Authors: Miguel Marin, Eloisa Jantus-Lewintre, Libia Sanz, Angel Garcia-Martin, Cristina Reinoso, Isabel Benet, David Montaner, Juan M. Vaquerizas, Joaquin Dopazo, Juan J. Calvete, Javier Garcia-Conde
Journal: Blood (2005)
Optimum low dose CT screening interval for lung cancer: the answer from NELSON?
Authors: David R Baldwin, S W Duffy, A Devaraj, J K Field
Journal: Thorax (2016)

The Dutch–Belgium randomised controlled trial of low dose CT screening (NELSON) is nearing the time it will report on the primary outcome of lung cancer mortality. The research team has published unique and influential data on the probability of malignancy in indeterminate pulmonary nodules according to their volume, growth as measured by volume doubling time and whether they are newly detected on incident screens.1 ,2 The NELSON investigators address another important factor influencing effective low radiation dose computed tomography (LDCT) screening: the maximum time interval allowable between screens before there is an unfavourable stage shift in cancers detected by screening and the rate of missed ‘interval’ cancers increases.3 In NELSON, subjects were screened at baseline, and then 1, 3 and 5.5 years from baseline. This gave intervals of 1, 2 and 2.5 years. Following an interval of 2.5 years, there were significantly more late-stage screen-detected cancers than for the 1-year interval and there were more interval cancers (5 during 1 year, 19 during 2 years and 28 during 2.5 years), with more than half appearing in the last 6 months of the 2.5-year interval (figure 3).3 The authors make the specific conclusion that a 2.5-year interval after two incident screening rounds is likely to reduce the effectiveness of screening but are more circumspect about recommending a 1-year or 2-year interval.

In the paper, table 3 shows how the number of screen-detected early-stage cancers falls as the screening interval increases, with statistical significance reached for the 2.5-year interval versus the 1-year interval. It could be argued that there is a trend across the 1, 2 and …
IMPACT OF THE NORDIC HAMSTRING AND HIP EXTENSION EXERCISES ON HAMSTRING ARCHITECTURE AND MORPHOLOGY: IMPLICATIONS FOR INJURY PREVENTION
Authors: Matthew Bourne, Steven Duhig, Ryan Timmins, David Opar, Morgan Williams, Graham Kerr, Anthony Shield
Journal: British Journal of Sports Medicine (2017)

Background There has been significant interest in exploring the patterns of muscle activity in hamstring exercises, however, there is no research examining the architectural and morphological adaptations of these muscles to different exercise interventions. Objective To evaluate changes in biceps femoris long head (BF LH ) fascicle length and hamstring muscle size following Nordic hamstring exercise (NHE) or hip extension (HE) training. Design In this longitudinal study, participants were randomly allocated to one of three groups: 1) HE training (n=10), NHE training (n=10), or no training (CON) (n=10). BF LH fascicle length was assessed before, during (Week 5) and after the intervention with 2D-ultrasound. Hamstring muscle size was determined before and after training via magnetic resonance imaging. Setting Laboratory based. Patients (or Participants) Thirty recreationally active males (age, 22.0±3.6 years, height, 180.4±7 cm, weight, 80.8±11.1 kg). Intervention A 10-week progressive intensity strength program consisting exclusively of NHE, HE training, or a period of no training. Main Outcome Measurements BF LH fascicle length and hamstring muscle volumes. Results Compared to baseline , BF LH fascicles were lengthened in the HE and NHE groups at mid- ( d= 1.12–1.39, p&lt;0.001) and post-training ( d= 1.77–2.17, p&lt;0.001) with no difference observed between training groups ( d= 0.49–0.80, p=0.279–0.976). BF LH volume increased more for the HE than the NHE ( d= 1.03, p=0.037) and CON ( d= 2.24, p&lt;0.001) groups. Compared to the CON group, both exercises induced significant increases in semitendinosus volume ( d= 2.16–2.50, ≤0.002) which were not significantly different ( d= 0.69, p=0.239). Conclusions NHE and HE training both stimulate significant increases in BF LH fascicle length, however, HE training may be more effective for promoting hypertrophy in the BF LH .
Neurotoxicity from immune-checkpoint inhibition in the treatment of melanoma: a single centre experience and review of the literature
Authors: L. Spain, G. Walls, M. Julve, K. O’Meara, T. Schmid, E. Kalaitzaki, S. Turajlic, M. Gore, J. Rees, J. Larkin
Journal: Annals of Oncology (2016)
Hamstring injuries in elite Gaelic football: an 8-year investigation to identify injury rates, time-loss patterns and players at increased risk
Authors: Mark Roe, John C Murphy, Conor Gissane, Catherine Blake
Journal: British Journal of Sports Medicine (2016)

Hamstring injuries occur frequently in field sports, yet longitudinal information to guide prevention programmes is missing.Investigate longitudinal hamstring injury rates and associated time loss in elite Gaelic football, while identifying subgroups of players at increased risk.38 data sets from 15 elite male Gaelic football teams were received by the National Gaelic Athletic Association (GAA) Injury Surveillance Database between 2008 and 2015. Injury and exposure data were provided by the team's medical staff via an online platform.391 hamstring injuries were sustained accounting for 21% (95% CI 20.0% to 21.7%) of all injuries. Prevalence was 21% (95% CI 19.2% to 23.4%). Incidences were 2.2 (95% CI 1.9 to 2.4) per 1000 exposure hours, and 7.0 (95% CI 6.5 to 7.1) times greater in match play than in training. Typically each team sustained 9.0 (95% CI 7.0 to 11.0) hamstring injuries per season affecting the: bicep femoris belly (44%; 95% CI 39.4% to 48.7%); proximal musculotendinous junction (13%; 95% CI 9.8% to 16.3%); distal musculotendinous junction (12%; 95% CI 8.6% to 14.9%) and semimembranosis/semitendinosis belly (9%; 95% CI 6.3% to 11.7%). ∼36% (95% CI 31.5% to 41.0%) were recurrent injuries. Mean time loss was 26.0 (95% CI 21.1 to 33.0) days, which varied with age, injury type and seasonal cycle. Hamstring injuries accounted for 31% (95% CI 25.8% to 38.2%) of injury-related time loss. Previously injured players (rate ratio (RR)=3.3), players aged 18-20 years (IRR=2.3) or >30 years (RR=2.3), as well as defensive (IRR=2.0) and midfield players (RR=1.5), were most at risk of sustaining a hamstring injury. Comparisons of 2008-2011 with 2012-2015 seasons revealed a 2-fold increase in hamstring injury incidences. Between 2008 and 2015 training incidence increased 2.3-fold and match-play incidences increased 1.3-fold.Hamstring injuries are the most frequent injury in elite Gaelic football, with incidences increasing from 2008-2011 to 2012-2015. Tailoring risk management strategies to injury history, age and playing position may reduce the burden of hamstring injuries.
Validation of the PREMM<sub>1,2</sub> model for the prediction of MLH1/MSH2 germline mutation carriers in a population- based cohort of colorectal cancer (CRC) patients
Authors: J. Balmaña, F. Balaguer, E. W. Steyerberg, E. M. Stoffel, S. Castellví-Bel, M. Andreu, A. Castells, S. Syngal
Journal: Journal of Clinical Oncology (2007)

10545 Background: PREMM 1,2 is a predictive model for estimating the likelihood of finding a mutation in the MLH1 and MSH2 genes developed in a population at risk of Lynch syndrome (Balmaña et al. JAMA 2006). The EPICOLON cohort is a Spanish population-based series of 1222 patients with CRC (Piñol et al. JAMA 2005). Methods: All 1222 individuals underwent microsatellite instability (MSI) and immunohistochemistry (IHC) analysis for MLH1/MSH2. Patients whose tumours exhibited MSI or altered IHC underwent MLH1/MSH2 analysis (n=91). Sensitivity (Se), specificity, positive predictive value (PPV), and the areas under the receiver operating characteristics curves (AUC) for the PREMM 1,2 model were calculated and compared with the Edinburgh model (Barnetson et al. NEJM 2006) and the Revised Bethesda guidelines (RBG). Results: Three-hundred and ninety six individuals (32%) had a PREMM 1,2 score =5%, 287 (23%) fulfilled the RBG, and 75 (6%) had a Barnetson score =5%. A PREMM 1,2 score =5% and the RBG identified all carriers with deleterious mutations (n=8, Se=100%), while a Barnetson score =5% missed 2 mutation carriers (Se= 75%). For PREMM 1,2 and Barnetson scores =5% and fulfilment of the RBG, specificities were 68%, 94%, and 77%, respectively; and PPV were 2%, 8%, and 2.8%, respectively. The AUC was 0.93 (95% CI: 0.86–0.99) for the PREMM 1,2 model and 0.86 (95% CI: 0.66–1.04) for the Barnetson model. The predictions of carrying a mutation stratified into five groups based on PREMM 1,2 scores (&lt;5%, 5–9%, 10–19%, 20–39%, =40%) correlated reasonably with the presence of mutations (0%, 1%, 1%, 13%, and 22%, respectively). Conclusions: In a population of CRC patients, the PREMM 1,2 model identifies all mutation carriers of MSH2 and MLH1 using a cutoff of =5%. In addition, it provides quantification of risk that is useful to decide the strategy used for molecular evaluation and risk counselling of patients. No significant financial relationships to disclose.
Randomized Trial of Liposomal Amikacin for Inhalation in Nontuberculous Mycobacterial Lung Disease
Authors: Kenneth N. Olivier, David E. Griffith, Gina Eagle, John P. McGinnis, Liza Micioni, Keith Liu, Charles L. Daley, Kevin L. Winthrop, Stephen Ruoss, Doreen J. Addrizzo-Harris, Patrick A. Flume, Daniel Dorgan, Matthias Salathe, Barbara A. Brown-Elliott, Renu Gupta, Richard J. Wallace
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Lengthy, multidrug, toxic, and low-efficacy regimens limit management of pulmonary nontuberculous mycobacterial disease.In this phase II study, we investigated the efficacy and safety of liposomal amikacin for inhalation (LAI) in treatment-refractory pulmonary nontuberculous mycobacterial (Mycobacterium avium complex [MAC] or Mycobacterium abscessus) disease.During the double-blind phase, patients were randomly assigned to LAI (590 mg) or placebo once daily added to their multidrug regimen for 84 days. Both groups could receive open-label LAI for 84 additional days. The primary endpoint was change from baseline to Day 84 on a semiquantitative mycobacterial growth scale. Other endpoints included sputum conversion, 6-minute-walk distance, and adverse events.The modified intention-to-treat population included 89 (LAI = 44; placebo = 45) patients. The average age of the sample was 59 years; 88% were female; 92% were white; and 80 and 59 patients completed study drug dosing during the double-blind and open-label phases, respectively. The primary endpoint was not achieved (P = 0.072); however, a greater proportion of the LAI group demonstrated at least one negative sputum culture (14 [32%] of 44 vs. 4 [9%] of 45; P = 0.006) and improvement in 6-minute-walk test (+20.6 m vs. -25.0 m; P = 0.017) at Day 84. A treatment effect was seen predominantly in patients without cystic fibrosis with MAC and was sustained 1 year after LAI. Most adverse events were respiratory, and in some patients it led to drug discontinuation.Although the primary endpoint was not reached, LAI added to a multidrug regimen produced improvements in sputum conversion and 6-minute-walk distance versus placebo with limited systemic toxicity in patients with refractory MAC lung disease. Further research in this area is needed. Clinical trial registered with www.clinicaltrials.gov (NCT01315236).
GW26-e1814 Role of Monocyte/Macrophage in TRPV1 Ablation-Induced Renal Injury in Salt-Sensitive Hypertension
Authors: Youping Wang, Mingjun Zhu, Leilei Fan, Miaomiao Fan, Lin Cui, Xiaoxiao Wang, Shiyang Xie, Si Shen
Journal: Journal of the American College of Cardiology (2015)
Prognostic factors for local control in Ewing sarcoma (ES) in the Euro-EWING99 trial.
Authors: Dimosthenis Andreou, Andreas Ranft, Daniel Baumhoer, Hendrik Van Den Berg, Bénédicte Brichard, P.D.Sander Dijkstra, Hans Gelderblom, Georg Gosheger, Jendrik Hardes, Wolfgang Hartmann, Jarmila Kruseova, Ruth Ladenstein, Andreas Leithner, Michael Paulussen, Arne Streitbuerger, Beate Timmermann, Per-Ulf Tunn, Reinhard Windhager, Heribert Juergens, Uta Dirksen
Journal: Journal of Clinical Oncology (2016)

11026 Background: Local recurrence (LR) is associated with very poor prognosis in ES patients. We sought to identify factors associated with LR in patients undergoing multimodal treatment. Methods: Retrospective analyses of the files of 1207 patients with previously untreated ES registered in the Euro-EWING99 trial (NCT00020566) from centers in D, A, B, CH, CZ und NL between 1998 and 2009. The primary outcome was local recurrence-free survival (LRFS), defined as the interval between diagnostic biopsy and LR. A secondary outcome was overall survival (OS). Results: With a median follow-up of 3.9 years for all patients and 5.9 years for survivors, LRFS was 81.6% at 5 years; OS was 59.9%. Pelvic tumors (PT) (p < 0.0001), primary tumor volume ≥ 200ml (p < 0.0001), locoregional tumor extension (p = 0.005), primary metastases (p < 0.0001), tumor regression ≤ 90% after neoadjuvant treatment (NT) (p < 0.0001) and deviations from protocol treatment (p = 0.001) were associated with a poorer LRFS. Complete removal of the involved bone was associated with improved LRFS (p = 0.007) and OS (p = 0.001) in PT, but not extremity tumors (ET) (p = 0.068; p = 0.848). Patients with PT undergoing surgery (S) and local radiation (RT) had an improved LRFS compared to patients undergoing only S (p = 0.01) or RT only (p < 0.0001). No differences in LRFS between S and S + RT were found in chest wall (CWT) (p = 0.239) and ET (p = 0.957); both provided better local control compared to RT only (p = 0.007 and p = 0.037 for CWT; p = 0.0002 and p = 0.001 for ET). PT with > 90% histological response to NT had a higher LRFS after S + RT compared to S only (p = 0.04) (n = 118), but not PT with ≤ 90% response (p = 0.564) (n = 38). Intralesional resections were associated with a poorer LRFS than marginal resections (p = 0.009), which had a poorer LRFS compared to wide or radical resections (p = 0.0002). Patients with soft tissue infiltration prior to surgery had a poorer LRFS (p = 0.001) and OS (p < 0.0001). Additional RT did not improve LRFS compared to S alone in these patients (p = 0.799). Conclusions: PT were associated with a poorer LRFS in this study, but appear to benefit from a complete removal of the involved bone and additional RT, even in cases with > 90% response to NT. RT additional to S does not appear to influence LRFS in CWT and ET.
Severe Anemia in Malawian Children
Authors: Job Cj Calis, Kamija S Phiri, E Brian Faragher, Bernard J Brabin, Imelda Bates, Luis E Cuevas, Rob J de Haan, Ajib I Phiri, Pelani Malange, Mirriam Khoka, Paul Jm Hulshof, Lisette van Lieshout, Marcel Ghm Beld, Yik Y Teo, Kirk A Rockett, Anna Richardson, Dominic P Kwiatkowski, Malcolm E Molyneux, Michaël Boele van Hensbroek
Journal: New England Journal of Medicine (2008)

Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied.We conducted a case-control study of 381 preschool children with severe anemia (hemoglobin concentration, <5.0 g per deciliter) and 757 preschool children without severe anemia in urban and rural settings in Malawi. Causal factors previously associated with severe anemia were studied. The data were examined by multivariate analysis and structural equation modeling.Bacteremia (adjusted odds ratio, 5.3; 95% confidence interval [CI], 2.6 to 10.9), malaria (adjusted odds ratio, 2.3; 95% CI, 1.6 to 3.3), hookworm (adjusted odds ratio, 4.8; 95% CI, 2.0 to 11.8), human immunodeficiency virus infection (adjusted odds ratio, 2.0; 95% CI, 1.0 to 3.8), the G6PD-202/-376 genetic disorder (adjusted odds ratio, 2.4; 95% CI, 1.3 to 4.4), vitamin A deficiency (adjusted odds ratio, 2.8; 95% CI, 1.3 to 5.8), and vitamin B12 deficiency (adjusted odds ratio, 2.2; 95% CI, 1.4 to 3.6) were associated with severe anemia. Folate deficiency, sickle cell disease, and laboratory signs of an abnormal inflammatory response were uncommon. Iron deficiency was not prevalent in case patients (adjusted odds ratio, 0.37; 95% CI, 0.22 to 0.60) and was negatively associated with bacteremia. Malaria was associated with severe anemia in the urban site (with seasonal transmission) but not in the rural site (where malaria was holoendemic). Seventy-six percent of hookworm infections were found in children under 2 years of age.There are multiple causes of severe anemia in Malawian preschool children, but folate and iron deficiencies are not prominent among them. Even in the presence of malaria parasites, additional or alternative causes of severe anemia should be considered.
Feasibility of Interim PET-Adapted Therapy in HIV-Positive Patients with Advanced Hodgkin Lymphoma (HL): Sub-Analysis of SWOG S0816 Phase 2 Trial
Authors: Alexey V Danilov, Hongli Li, Oliver W. Press, Ilan Shapira, Lode J. Swinnen, Ariela Noy, Erin Reid, Sonali M. Smith, Jonathan W. Friedberg
Journal: Blood (2015)
Heterogeneous expression of prognostic and predictive antigens in primary and metastatic gastric cancer
Authors: M. Joka, K. Pietsch, S. Paulick, R. Issels, K. Jauch, B. Mayer
Journal: Journal of Clinical Oncology (2009)

e22030 Background: Metastatic spread of cancer cells is a key event in tumor progression and in determining the prognosis of patients with malignant disease. This study evaluated the expression of prognostic and predictive molecules in primary and metastatic gastric cancer. Our objectives were to correlate the expression pattern with the clinicopathological features and patient survival and confirm the results using a coculture spheroid model. Methods: The clinicopathological features of 94 patients (57,4% male, 42,6% female, median age of 66,2 years) with gastric cancer were characterized using multivariate and univariate analysis. Further we compared the expression profile of biomarkers, namely EPCAM, CD44s, HLA-ABC and the associated β chain, HLA-DR, ICAM-1, LFA-3 and E-Cadherin in primary gastric tumors (n=94) and their synchronous metastases (regional lymph nodes n=32, liver n=14, peritoneum n=17) using immunoperoxidase staining. A coculture in vitro model, i.e. the homo- and heterotypic spheroid model were performed as a functional test system to confirm the microenvironmental impact on the biomarker expression level. Results: Strong HLA-ABC expression was found in both primary and metastatic tumors. High expression of HLA-ABC in liver metastases significantly correlated with metastatic disease (UICC TNM stage IV, p=0,026). Contrary, the detection of HLA-DR on the cancer cells correlated with the degree of the inflammatory infiltrate (CD45, p=0,019). With respect to CD44s, the prognostic marker was upregulated in the metastatic tumors independently of their localisation (p=0.009) compared to the primary lesions. E-cadherin and LFA-3 expression were preferentially increased in distant metastases, but not in locally advanced gastric tumors (liver: E-cadherin, p=0.001; liver and peritoneum: LFA-3, p=0.0067). E-cadherin expression was upregulated in the heterotypic spheroid model coculturing primary liver cells and N87 gastric cancer cells (80% E-cadherin positive N87 cells) compared to the homotypic spheroid model consisting of N87 cells alone (40% E-cadherin positive N87 cells). Conclusions: These data suggest the consideration of the metastatic protein profile for the selection of cancer patients in new molecular therapeutic strategies. No significant financial relationships to disclose.
The Persistence of p190 BCR-ABL Transcripts Is Associated with Lower Probability of Molecular Response to Imatinib in Early and Late Chronic Phase CML Patients.
Authors: Anna Garuti, Adalberto Ibatici, Gabriella Cirmena, Maurizio Miglino, Riccardo Varaldo, Colombo Nicoletta, Roberta Grasso, Sarah Pozzi, Marina Podesta, Marco Gobbi, Mario Sessarego, Franco Patrone, Francesco Frassoni
Journal: Blood (2005)
Clinical and pathologic characteristics of Hispanic breast cancer patients in a tertiary care safety net hospital.
Authors: T. M. Lee, L. A. Stead, M. M. Loch, J. L. Westrup, M. Hernandez-Perez, J. C. Lee, A. de las Morenas, T. P. Ahern, C. L. Rosenberg
Journal: Journal of Clinical Oncology (2010)

1591 Background: Data on breast cancers (BrCa) in the Hispanic population are limited. We studied patient and tumor characteristics of Hispanic BrCa patients (pts) in an ethnically diverse, predominantly low socioeconomic status, tertiary care hospital. Methods: We expanded our established database to include all women diagnosed at our institution with invasive BrCa from 1998-2008. From the electronic medical record, we recorded age, body mass index (BMI) and menopausal status at diagnosis, family and personal history of cancer, self- identified ethnic group, place of birth, ER, PR, Ki67, HER2 expression, grade and TNM stage. We compared characteristics across race/ethnicity categories with cross-tabular chi-square analyses and univariate and multivariate logistic and linear regression models. Results: 647 cases were identified (37% white [W], 42% black [B], 11% Hispanic [H], 10% other [O]). This analysis focuses on the 3 defined racial/ethnic groups. H pts were younger at diagnosis, mean ages = 54.8, 58.3, 61.8 for H, B, W, respectively (p across groups < 0.001). H pts had a higher proportion of ER+/PR+ tumors, 80.6%, 53.0%, 73.6% for H, B, W, respectively, even after adjustment for BMI and age at diagnosis (p < 0.0001). The absolute % ER/PR positivity per case did not differ across groups (mean %s = 71.9/59.4), and we saw no associations between age at diagnosis and either BMI or ER/PR status (others' data has shown an increase in ER+ tumors with advancing age). Triple-negative tumors were less common in H than B pts, OR = 0.27 (p = 0.004), and grade was lower in H than B pts (p = 0.04). Rates of both were equivalent in H and W pts. A personal history of cancer was less common in H than W (but not B) pts, OR = 0.53, even after adjustment for age (p = 0.0006). Family history did not differ in H compared to W or B pts. BMI (mean = 30.3), T and N stage, HER2 and Ki67 expression did not differ in H compared to either B or W pts. Conclusions: H pts were younger at BrCa diagnosis, but had favorable features - less personal history, more ER+/PR + tumors, no excess of high-grade or triple-negative tumors. BrCa in our H pts may reflect a distinct BrCa subtype. No significant financial relationships to disclose.