tbuckley/cabot-search huggingface dataset:
Long-term outcomes of hypoxia modification in bladder preservation: Update from BCON trial.
Authors: Yee Pei Song, Hitesh Mistry, Ananya Choudhury, Peter Hoskin
Journal: Journal of Clinical Oncology (2019)

356 Background: The mainstay of radical organ preserving treatment in muscle-invasive bladder cancer is radiotherapy (RT). Radiosensitising agents have been shown to improve treatment response and survival. Chemoradiotherapy is the most commonly used regime, however, hypoxia modification has also been shown to be effective. BCON is a phase III clinical trial which showed that the addition of carbogen and nicotinamide (CON) significantly improved recurrence-free survival (RFS) and overall survival (OS) (Hoskin et al, 2010). The long term outcomes twelve years after the trial closed to recruitment are reported. Methods: Outcomes from the original BCON trial were updated and analysed. Patients excluded from the original analysis were excluded once again. Cox regression analysis adjusted for known prognostic factors was performed. Results: 333 patients were randomized to receive RT alone or RT+CON. 9 patients from the RT+CON arm and 3 from RT alone arm were excluded from the analysis. The median age of patients in both arms was 74 (51-90) and the median follow-up was 10.3 years. There was a statistically significant improvement in 5 year RFS (41% vs 33%, p = 0.04) with the difference maintained at 10 years (27% vs 20%). The 5 year OS was 49% vs 40% (p = 0.068) with a continued effect seen at 10 years when OS was 32% vs 24%. These differences remained following adjustment for known prognostic factors. Conclusions: The survival advantage for CON in the original analysis which demonstrated a significantly improved 3 years OS (59% vs 47%, p = 0.020) is maintained in long term follow up. At 5 years there is a statistically significant improvement in RFS and at 5 and 10 years the addition of hypoxia modification to radiotherapy continues to show an impact on overall survival, These results confirm a sustained benefit of hypoxia modification in bladder preservation treatment for muscle-invasive bladder cancer. Clinical trial information: NCT00033436.
Abstract P424: Worksite Food Purchases Are Associated With Employees’ Overall Dietary Intake and Health
Authors: Jessica L McCurley, Douglas E Levy, Eric B Rimm, Emma M Anderson, Jenny M Sanford, Emily D Gelsomin, Anne N Thorndike
Journal: Circulation (2019)

Introduction: Most Americans spend half their waking hours at work. We hypothesized that the healthfulness of worksite food purchases was associated with employees’ overall dietary intake and cardiometabolic health. Methods: Participants were 602 hospital employees who regularly used worksite cafeterias and enrolled in a worksite nutrition study in 2016-18. All hospital cafeterias used traffic-light labels (green = healthy, yellow = less healthy, red = unhealthy). We calculated the proportion of participants’ green- and red-labeled items purchased during a 3 month baseline period. Participants completed 2 online Automated Self-Administered 24-hour dietary recalls used to calculate a baseline Healthy Eating Index (HEI) score (range 0-100, higher = healthier diet). Additional baseline measures included BMI, blood pressure (BP), and HbA1c. Hypertension (HTN) and prediabetes/diabetes (pre-DM/DM) diagnoses were determined by self-report and/or medication use and/or baseline measures (HTN: systolic BP ≥ 150 mmHg or diastolic BP ≥ 90 mmHg; pre-DM/DM: Hb A1c ≥ 5.7). Linear and logistic regression analyses examined differences in HEI scores and cardiometabolic variables by tertiles of green- or red-labeled purchases, adjusting for age, sex, race, ethnicity, education, and number of purchases. Results: Mean age of participants was 43.6 yrs; 79% (N=478) were female and 81% (N=488) white. Mean BMI was 28.3 kg/m 2 (SD: 6.5), 63% (N=377) were overweight/obese, 21% (N=124) had HTN, and 27% (N=160) had pre-DM/DM. Mean number of items purchased during the observation period was 112 (SD: 21); mean baseline HEI score was 60.4 (SD: 12.5). The table shows that proportions of green and red items purchased were associated with diet quality (HEI score) and cardiometabolic risk (BMI, HTN, DM). Conclusions: Food purchases at work were associated with employees’ overall diet quality and cardiometabolic risk factors. Results suggest that interventions to promote healthier worksite food choices have potential to impact overall health.
Clinical activity of ipilimumab plus nivolumab (Ipi/Nivo) in patients (pts) with metastatic non-clear cell renal cell carcinoma (nccRCC).
Authors: Ruby Gupta, Moshe Chaim Ornstein, Anita Gul, Kimberly D Allman, Jessica Ball, Laura S. Wood, Jorge A. Garcia, Dendra VonMerveldt, Hans J. Hammers, Brian I. Rini
Journal: Journal of Clinical Oncology (2019)

e16084 Background: Ipi/Nivo is a standard of care for pts with metastatic clear cell RCC. The clinical activity of Ipi/Nivo in patients with metastatic nccRCC remains poorly defined. Methods: Metastatic nccRCC pts who were treated with Ipi/Nivo at Cleveland Clinic or UT Southwestern were retrospectively reviewed. Ipi/Nivo was administered as per CHECKMATE 214. Computed tomography imaging was obtained at baseline and every 12 weeks to assess disease response per RECIST 1.1 criteria. Baseline pt characteristics, outcome to therapy and adverse effects as per CTCAE v5.0 were collected. Results: Eighteen pts with metastatic nccRCC histology who were treated with Ipi/Nivo were identified. The median age was 60 years (range, 32-81). Non clear cell histologies included adenocarcinoma of renal origin not otherwise specified (2), unclassified (3), papillary (6), chromophobe (5), translocation (1) and medullary histology (1). ECOG PS was 0 (7 pts); 1 (9 pts) and 2 (2 pts). Fourteen patients were male and four female. IMDC risk group at the time of initiation of Ipi/Nivo was favorable (2 pts), intermediate (14 pts) and poor (2 pt). Fourteen pts received Ipi/ Nivo as first line treatment, two pts received Ipi/Nivo after prior TKI and two pts received Ipi/ Nivo as third line treatment after prior chemotherapy and nivolumab monotherapy. In total, fourteen pts had restaging scans with four pts demonstrating partial response (PR 28%), two with stable disease (SD 14%) and eight with progressive disease (PD 58%). Four pts died (22%) – three from the disease and one from treatment related complication (encephalitis).Four pts experienced diarrhea- three pts (grade 2) and one pt ( grade 3) , three developed hepatotoxicity- one pt (grade 2) and two pts (grade 3), one pt each developed hypophysitis (grade 3), fatigue (grade 2) , rash (grade 2) and encephalitis (grade 3). All 100% pts required steroids, one each got infliximab and Mycophenolate Mofetil. . All 100% pts required steroids, one each got infliximab and Mycophenolate Mofetil. Conclusions: Ipi/Nivo is feasible and safe in patients with metastatic nccRCC with preliminary evidence of anti-tumor activity
NHS hospitals could be fined if they miss new sepsis targets
Authors: Gareth Iacobucci
Journal: BMJ (2019)

NHS hospitals in England could face fines if they fail to adhere to new guidelines1 for detecting and treating adult sepsis.

The mandatory guidance requires hospital staff to alert senior doctors if patients with suspected sepsis do not respond to treatment within an hour. All NHS trusts in England will be contractually obliged to comply with the new guidance from 1 April.

The advice—drawn up by the NHS with the Royal College of Physicians, the Royal College of General Practitioners, the National Institute for Health and Care Excellence (NICE), and the UK Sepsis Trust—follows a commitment …
Intrinsic Variable Learning for Brain-Machine Interface Control by Human Anterior Intraparietal Cortex
Authors: Sofia Sakellaridi, Vassilios N. Christopoulos, Tyson Aflalo, Kelsie W. Pejsa, Emily R. Rosario, Debra Ouellette, Nader Pouratian, Richard A. Andersen
Journal: Neuron (2019)
Cardiopulmonary Effects of Fine Particulate Matter Exposure among Older Adults, during Wildfire and Non-Wildfire Periods, in the United States 2008–2010
Authors: Stephanie DeFlorio-Barker, James Crooks, Jeanette Reyes, Ana G. Rappold
Journal: Environmental Health Perspectives (2019)

The effects of exposure to fine particulate matter ([Formula: see text]) during wildland fires are not well understood in comparison with [Formula: see text] exposures from other sources. We examined the cardiopulmonary effects of short-term exposure to [Formula: see text] on smoke days in the United States to evaluate whether health effects are consistent with those during non-smoke days. We examined cardiopulmonary hospitalizations among adults [Formula: see text] y of age, in U.S. counties ([Formula: see text]) within [Formula: see text] of 123 large wildfires during 2008-2010. We evaluated associations during smoke and non-smoke days and examined variability with respect to modeled and observed exposure metrics. Poisson regression was used to estimate county-specific effects at lag days 0-6 (L0-6), adjusted for day of week, temperature, humidity, and seasonal trend. We used meta-analyses to combine county-specific effects and estimate overall percentage differences in hospitalizations expressed per [Formula: see text] increase in [Formula: see text]. Exposure to [Formula: see text], on all days and locations, was associated with increased hospitalizations on smoke and non-smoke days using modeled exposure metrics. The estimated effects persisted across multiple lags, with a percentage increase of 1.08% [95% confidence interval (CI): 0.28, 1.89] on smoke days and 0.67% (95% CI: [Formula: see text], 1.44) on non-smoke days for respiratory and 0.61% (95% CI: 0.09, 1.14) on smoke days and 0.69% (95% CI: 0.19, 1.2) on non-smoke days for cardiovascular outcomes on L1. For asthma-related hospitalizations, the percentage increase was greater on smoke days [6.9% (95% CI: 3.71, 10.11)] than non-smoke days [1.34% (95% CI: [Formula: see text], 3.77)] on L1. The increased risk of [Formula: see text]-related cardiopulmonary hospitalizations was similar on smoke and non-smoke days across multiple lags and exposure metrics, whereas risk for asthma-related hospitalizations was higher during smoke days. https://doi.org/10.1289/EHP3860.
Everolimus in patients with metastatic renal cell carcinoma (RCC) previously treated with bevacizumab: Final results of prospective multicenter study.
Authors: Anton Snegovoy, Sergey Varlamov, Sufia Safina, Ilya Varlamov, Ludmila Gurina, Liudmila V. Manzyuk, Ilya Tsimafeyeu
Journal: Journal of Clinical Oncology (2015)

e15621 Background: Everolimus provides a consistent clinical benefit in the treatment of patients with metastatic RCC who progressed on previous TKI treatment. The aim of this study is to evaluate the efficacy and toxicity profile of the everolimus after bevacizumab ± IFN, reporting the final results of progression-free survival (PFS), overall survival (OS) and the toxicity experienced. Methods: In open-label, single-arm, multicenter clinical trial patients were enrolled between December 2011 and October 2013, with follow-up continuing until disease progression, unacceptable toxicity, or withdrawal of consent. Patients had metastatic clear-cell RCC, which had progressed despite previous bevacizumab ± IFN therapy. Everolimus, 10 mg per day given orally daily. The primary endpoint was overall response rate. Secondary endpoints were PFS, OS and safety. Results: 37 patients were accrued. Patients were predominantly male, 89% had ECOG performance status of 0/1, 51% received previous bevacizumab in combination with IFN, and 38/62% had MSKCC favorable/intermediate risk disease. The median duration of treatment was 315 (range 61–569) days. Confirmed objective tumor responses (all partial responses) were seen in five (14%) patients. 70% patients had a stable disease. Median PFS was 11.5 months (95% CI, 8.8-14.2). Median overall survival was 17.4 months (95% CI, 13.5-21.3). No grade 3 or 4 treatment-related toxicities were observed. The most common grade 2 adverse events were fatigue (19%) and pneumonitis (8%). Conclusions: The results of this trial demonstrate the efficacy and manageable adverse-event profile of everolimus as a single agent in second-line therapy for patients with metastatic clear-cell RCC who progressed on previous bevacizumab ± IFN treatment. Clinical trial information: NCT02056587.
Safety and efficacy of sonothrombolysis for acute ischaemic stroke: a multicentre, double-blind, phase 3, randomised controlled trial
Authors: Andrei V Alexandrov, Martin Köhrmann, Lauri Soinne, Georgios Tsivgoulis, Andrew D Barreto, Andrew M Demchuk, Vijay K Sharma, Robert Mikulik, Keith W Muir, Gordon Brandt, John Alleman, James C Grotta, Christopher R Levi, Carlos A Molina, Maher Saqqur, Dimitris Mavridis, Theodora Psaltopoulou, Milan Vosko, Jochen B Fiebach, Pitchaiah Mandava, Thomas A Kent, Anne W Alexandrov, Peter D Schellinger
Journal: The Lancet Neurology (2019)
Abstract P330: Excluding Participants With Missing or Incomplete Accelerometry Data: Evaluating the Potential for Bias
Authors: Erin Delker, Laura Pampano, John Bellettiere
Journal: Circulation (2019)

Background: Investigating the effect of physical activity (PA) on health has been improved with accelerometry. However, accelerometer measurement may increase participant burden, leading some to not wear devices. Previous research suggests that participants who do not wear accelerometers may be less active and have worse health outcomes than those who adhere to measurement protocol. This selection bias may lead to underestimates of the true association between PA and CVD outcomes. Using simulations, we illustrate how the association of meeting WHO PA guidelines and hypertension (HT) might be impacted by missing accelerometry data. Methods: Based on observed prevalence of PA and HT in an ongoing cohort study, we simulated data with 2000 participants, with 40% not meeting PA guidelines and 10% having HT. We set the “true” association between not meeting PA guidelines and HT at 1.9 (OR=1.9; 95% CI=1.5, 2.5). Then, we simulated scenarios to show the impact of four different patterns of missing accelerometer data: A) Missingness independent of PA and HT; B) Missingness associated with PA only; C) Missingness associated with HT only; D) Missingness associated with PA and HT. For each scenario, we conducted complete cases analyses using simple logistic regression to assess associations between meeting PA guidelines and HT. Results: Odds ratios (ORs) in Scenarios A, B, and C were unbiased. ORs in Scenario D underestimated the magnitude of the “true” association and were increasingly attenuated as the strength of the relationship between study variables and missingness was increased. Conclusions: Accelerometer measurement may result in missing data, which can bias odds ratio estimates if the missingness is associated with both the exposure and outcome, a scenario reported in previous research. Efforts to minimize missing data during study design should be prioritized. Carefully considering the structure of missingness in analyses will inform quantification of potential bias, analytic strategies, and interpretation of findings.
MiR-145 mediates cell morphology-regulated mesenchymal stem cell differentiation to smooth muscle cells
Authors: Yi-Ting Yeh, Josh Wei, Satenick Thorossian, Katherine Nguyen, Clarissa Hoffman, Juan C. del Álamo, Ricardo Serrano, Yi-Shuan Julie Li, Kuei-Chun Wang, Shu Chien
Journal: Biomaterials (2019)

The use of biochemical signaling to derive smooth muscle cells (SMCs) from mesenchymal stem cells (MSCs) has been explored, but the induction of a fully functional SMC phenotype remains to be a major challenge. Cell morphology has been shown to regulate MSC differentiation into various lineages, including SMCs. We engineered substrates with microgrooves to induce cell elongation to study the mechanism underlying the MSC shape modulation in SMC differentiation. In comparison to those on flat substrates, MSCs cultured on engineered substrates were elongated with increased aspect ratios for both cell body and nucleus, as well as augmented cytoskeletal tensions. Biochemical studies indicated that the microgroove-elongated cells expressed significantly higher levels of SMC markers. MicroRNA analyses showed that up-regulation of miR-145 and the consequent repression of KLF4 in these elongated cells promoted MSC-to-SMC differentiation. Rho/ROCK inhibitions, which impair cytoskeletal tension, attenuated cell and nuclear elongations and disrupted the miR-145/KLF4 regulation for SMC differentiation. Furthermore, cell traction force measurements showed that miR-145 is essential for the functional contractility in the microgroove-induced SMC differentiation. Collectively, our findings demonstrate that, through a Rho-ROCK/miR-145/KLF4 pathway, the elongated cell shape serves as a decisive geometric cue to direct MSC differentiation into functional SMCs.
Breast cancer in male AYA.
Authors: Rashmi Bawa, Devin C. Flaherty, Claire Sadler, Melanie Goldfarb
Journal: Journal of Clinical Oncology (2015)

1578 Background: Breast cancer is one of the most common cancers in female adolescent and young adults (AYA: ages 15-39 years), which may develop de novo or in patients previously treated for cancer. However, there is scant data about primary or secondary (SMN) male breast cancer in AYAs. This study investigates factors effecting the overall survival (OS) of male breast AYA and compares the demographic, tumor, treatment characteristics, and OS of primary versus SMN in this population. Methods: All 589 cases of invasive AYA male breast cancer in the 1998-2010 American College of Surgeons National Cancer Database were examined. Kaplan-Meier with log-rank test and Cox-proportional regression analyses analyzed OS in the entire cohort. Patients were divided into two groups according to primary or secondary occurrence and compared with appropriate statistical methods. Results: For the entire cohort, non-white race (p = 0.004), government/military/medicare or no insurance (p < .001), lower socioeconomic status (SES) (p = .026), larger tumor size (p = 0.034), distant metastases (p < .001), not having any surgery (p < .001) or no nodal surgery (p < .001) all led to worse OS. On multivariate regression, tumor size (HR 1.02, CI 1.01-1.03), distant metastases (HR 4.95, CI 2.23-10.99), and lower SES (HR 2.15, CI: 1.31-3.49) had worse OS. 35 patients (5.9%) had a SMN, with similar demographic, tumor and treatment characteristics (when stratified by stage) to primary male breast cancers. However, there was a trend for SMN patients to present with less nodal disease (0.063), receive less radiation (p = 0.068), and occur less commonly in Blacks (p = 0.084). 3-year OS was 86.3% for primary cancer and 76.2% for SMN patients (p = 0.20). SMN patients without insurance (p = 0.035), with distant metastases (p = 0.048), and not having nodal surgery (p = 0.008) had worse OS. Conclusions: Larger tumor size, distant metastasis and lower SES are associated with worse OS in male AYAs with breast cancer. Outcomes are similar regardless of primary or secondary tumor status.
Nocturnal Melatonin Renews Bone and Blood Forming Stem Cells Reservoir By Metabolic Reprograming
Authors: Karin Golan, Mayla Bertagna, Suditi Bhattacharya, Anoop Babu-Vasandan, Francesca Avemaria, Eman Khatib-Massalha, Zulma S. Ferreira, Orit Kollet, Abraham Avigdor, Regina P. Markus, Tsvee Lapidot
Journal: Blood (2018)
Elimination, not reduction: Lessons from the Research Domain Criteria (RDoC) and multiple realisation
Authors: Tuomas K. Pernu
Journal: Behavioral and Brain Sciences (2019)

Abstract The thesis of multiple realisation that Borsboom et al. are relying on should not be taken for granted. In dissolving the apparent multiple realisation, the reductionist research strategies in psychopathology research (the Research Domain Criteria [RDoC] framework, in particular) are bound to lead to eliminativism rather than reductionism. Therefore, Borsboom et al. seem to be aiming at a wrong target.
Effect of Catheter Ablation vs Antiarrhythmic Medication on Quality of Life in Patients With Atrial Fibrillation
Authors: Carina Blomström-Lundqvist, Sigfus Gizurarson, Jonas Schwieler, Steen M. Jensen, Lennart Bergfeldt, Göran Kennebäck, Aigars Rubulis, Helena Malmborg, Pekka Raatikainen, Stefan Lönnerholm, Niklas Höglund, David Mörtsell
Journal: JAMA (2019)

Quality of life is not a standard primary outcome in ablation trials, even though symptoms drive the indication.To assess quality of life with catheter ablation vs antiarrhythmic medication at 12 months in patients with atrial fibrillation.Randomized clinical trial at 4 university hospitals in Sweden and 1 in Finland of 155 patients aged 30-70 years with more than 6 months of atrial fibrillation and treatment failure with 1 antiarrhythmic drug or β-blocker, with 4-year follow-up. Study dates were July 2008-September 2017. Major exclusions were ejection fraction <35%, left atrial diameter >60 mm, ventricular pacing dependency, and previous ablation.Pulmonary vein isolation ablation (n = 79) or previously untested antiarrhythmic drugs (n = 76).Primary outcome was the General Health subscale score (Medical Outcomes Study 36-Item Short-Form Health Survey) at baseline and 12 months, assessed unblinded (range, 0 [worst] to 100 [best]). There were 26 secondary outcomes, including atrial fibrillation burden (% of time) from baseline to 12 months, measured by implantable cardiac monitors. The first 3 months were excluded from rhythm analysis.Among 155 randomized patients (mean age, 56.1 years; 22.6% women), 97% completed the trial. Of 79 patients randomized to receive ablation, 75 underwent ablation, including 2 who crossed over to medication and 14 who underwent repeated ablation procedures. Of 76 patients randomized to receive antiarrhythmic medication, 74 received it, including 8 who crossed over to ablation and 43 for whom the first drug used failed. General Health score increased from 61.8 to 73.9 points in the ablation group vs 62.7 to 65.4 points in the medication group (between-group difference, 8.9 points; 95% CI, 3.1-14.7; P = .003). Of 26 secondary end points, 5 were analyzed; 2 were null and 2 were statistically significant, including decrease in atrial fibrillation burden (from 24.9% to 5.5% in the ablation group vs 23.3% to 11.5% in the medication group; difference -6.8% [95% CI, -12.9% to -0.7%]; P = .03). Of the Health Survey subscales, 5 of 7 improved significantly. Most common adverse events were urosepsis (5.1%) in the ablation group and atrial tachycardia (3.9%) in the medication group.Among patients with symptomatic atrial fibrillation despite use of antiarrhythmic medication, the improvement in quality of life at 12 months was greater for those treated with catheter ablation compared with antiarrhythmic medication. Although the study was limited by absence of blinding, catheter ablation may offer an advantage for quality of life.clinicaltrialsregister.eu Identifier: 2008-001384-11.