tbuckley/cabot-search huggingface dataset:
Targeted DNA and RNA Sequencing of Paired Urothelial and Squamous Bladder Cancers Reveals Discordant Genomic and Transcriptomic Events and Unique Therapeutic Implications
Authors: Daniel H. Hovelson, Aaron M. Udager, Andrew S. McDaniel, Petros Grivas, Phillip Palmbos, Shuzo Tamura, Lorena Lazo de la Vega, Ganesh Palapattu, Brendan Veeneman, Layla El-Sawy, Seth E. Sadis, Todd M. Morgan, Jeffrey S. Montgomery, Alon Z. Weizer, Kathleen C. Day, Nouri Neamati, Monica Liebert, Evan T. Keller, Mark L. Day, Rohit Mehra, Scott A. Tomlins
Journal: European Urology (2018)
Bioprinting: Inkjet–Spray Hybrid Printing for 3D Freeform Fabrication of Multilayered Hydrogel Structures (Adv. Healthcare Mater. 14/2018)
Authors: Sejeong Yoon, Ju An Park, Hwa‐Rim Lee, Woong Hee Yoon, Dong Soo Hwang, Sungjune Jung
Journal: Advanced Healthcare Materials (2018)

In article 1800050, Sungjune Jung and co-workers present a new bioprinting process by combining drop-on-demand inkjet printing with a spray-coating technique. Successfully fabricated hydrogel structures with various shapes, sizes and materials, including alginate, cellulose nanofiber, fibrinogen, and gelatine methacryloyl-based bioinks that are inkjet-printable are presented. The proposed printing technique and the bioinks can be used to produce large-scale, 3D laminated structures that potentially include the functions of native tissues such as skin and epithelium.
Myocyte Death, Growth, and Regeneration in Cardiac Hypertrophy and Failure
Authors: BernardoNadal-Ginard, JanKajstura, AnnarosaLeri, PieroAnversa
Journal: Circulation Research (2003)

The accepted paradigm considers the adult mammalian heart as a postmitotic organ, which possesses a relatively constant number of myocytes from shortly after birth to adulthood and senescence. This notion is questioned by the demonstration that although most adult myocytes are terminally differentiated, there is a small and continuously renewed subpopulation of cycling myocytes produced by the differentiation of cardiac stem-like cells. Myocyte death and myocyte regeneration are introduced as major determinants of cardiac homeostasis and alterations of ventricular anatomy and function in physiological and pathological states. The possibility of reconstituting dead myocardium by stem-like cells is advanced and proposed as a major area of future research.
Genetic and Environmental Contributions to Childhood Growth in Stature and Lifetime Overweight Risk.
Authors: Stefan A Czerwinski, Jeff T Williams, Wayne Wisemandle, Bradford Towne, Ellen W Demerath, Shumei S Guo, Wm. Cameron Chumlea, Roger M Siervogel
Journal: Circulation (2001)

P09     The prevalence of childhood overweight and obesity in the US  continues to increase. Epidemiological studies have shown that children  who mature earlier tend to have an increased risk of being overweight  in adulthood. Acknowledging that measures of overweight and patterns of  human growth are under moderate to strong genetic control, we examined  the nature of these associations using a bivariate variance components  approach to estimate the genetic and environmental correlations between  lifetime overweight status and parameters of the adolescent growth  spurt. Serial stature data from 490 participants in the Fels  Longitudinal Study were used to derive three adolescent growth curve  parameters: peak height velocity (PHV), age at PHV, and height at PHV.  Three categories of lifetime overweight status were determined from  over 16,000 serial observations according to age at onset of  overweight: early-onset overweight (BMI >25 kg/m   2    before  age 25 y), late-onset overweight (BMI >25 kg/m   2    after  age 25 y), and never overweight (never having a BMI measurement  >25 kg/m   2   ). Those classified as overweight also needed to  meet certain criteria (i.e., maintenance of BMI >25 kg/m   2   in 80% of all subsequent visits following the first presentation).  Heritability estimates (h   2   ) for the adolescent growth  parameters are h   2   =0.54 for PHV, h   2   =0.74 for age  at PHV, and h   2   =0.92 for height at PHV. Heritability  estimates for lifetime overweight status range from 0.52-0.57 depending  upon the age at onset categorization. Although all of the traits  examined are highly heritable, preliminary analyses reveal little  effect of shared genes between the adolescent growth curve parameters  and the lifetime overweight status categories; the genetic correlations  are low and insignificant. There is, however, a statistically  significant negative environmental correlation (ρ   e   =-0.40)  between age at PHV and the lifetime overweight status category  contrasting never overweight with early/late overweight. These results  suggest that environmental influences on the timing of the adolescent  growth spurt may be more influential in predicting adult risk of  overweight than shared genetic factors.
Comparing the different diagnostic criteria of Asthma‐COPD overlap
Authors: Yong Suk Jo, Yong Il Hwang, Kwang Ha Yoo, Tae‐Hyung Kim, Myung Goo Lee, Sang Haak Lee, Kyeong‐Cheol Shin, Kwang Ho In, Hyoung Kyu Yoon, Chin Kook Rhee
Journal: Allergy (2018)

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A 26-Week Randomized Controlled Trial of Semaglutide Once Daily Versus Liraglutide and Placebo in Patients With Type 2 Diabetes Suboptimally Controlled on Diet and Exercise With or Without Metformin
Authors: Ildiko Lingvay, Cyrus V. Desouza, Katarina S. Lalic, Ludger Rose, Thomas Hansen, Jeppe Zacho, Thomas R. Pieber
Journal: Diabetes Care (2018)

OBJECTIVE To investigate the efficacy and safety of once-daily semaglutide in comparison with once-daily liraglutide and placebo in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS This 26-week, multicenter, double-blind trial involved patients diagnosed with type 2 diabetes with HbA1c 7.0–10.0% (53–86 mmol/mol) and treated with diet and exercise with or without metformin. Patients were randomized 2:2:1 to once-daily semaglutide, liraglutide, or placebo in one of four volume-matched doses (semaglutide 0.05, 0.1, 0.2, or 0.3 mg and liraglutide 0.3, 0.6, 1.2, or 1.8 mg, with both compared within each volume-matched dose group). Primary end point was change in HbA1c from baseline to week 26. RESULTS In total, 705 randomized patients were exposed to trial products. At week 26, a dose-dependent change in HbA1c was observed with semaglutide from −1.1% (0.05 mg) to −1.9% (0.3 mg) and with liraglutide from −0.5% (0.3 mg) to −1.3% (1.8 mg) (all P &amp;lt; 0.001 in favor of volume-matched semaglutide dose). Change with pooled placebo was −0.02% (P &amp;lt; 0.0001 vs. semaglutide). Gastrointestinal (GI) disorders were the most common adverse events (AEs) with semaglutide and liraglutide, occurring in 32.8–54.0% and 21.9–41.5% of patients, respectively. CONCLUSIONS Once-daily semaglutide at doses up to 0.3 mg/day resulted in greater reductions in HbA1c compared with liraglutide or placebo but with a higher frequency of GI AEs.
Beneficial Effects of Intracoronary Adenosine as an Adjunct to Primary Angioplasty in Acute Myocardial Infarction
Authors: MarioMarzilli, EnricoOrsini, PaoloMarraccini, RobertoTesta
Journal: Circulation (2000)

Background—The benefits of vessel recanalization in acute myocardial infarction (AMI) are limited by reperfusion damage. In animal models, adenosine limits reperfusion injury, reducing infarct size and improving ventricular function. The aim of this study was to evaluate the safety and feasibility of adenosine adjunct to primary PTCA in AMI. Methods and Results—Fifty-four AMI patients undergoing primary PTCA were randomized to intracoronary adenosine or saline. The 2 groups were similar for age, sex, and infarct location. Adenosine administration was feasible and well tolerated. PTCA was successful in all patients and resulted in TIMI 3 flow in all patients given adenosine and in 19 given saline (P<0.05). The no-reflow phenomenon occurred in 1 adenosine patient and in 7 saline patients (P=0.02). Creatine kinase was lower in the adenosine group, and a Q-wave MI developed in 16 adenosine patients and in 23 saline patients (P=0.04). Sixty-four percent of dyssynergic segments improved in the adenosine group a...
Lack of public health resources leaves London vulnerable to pandemic, BMA warns
Authors: Gareth Iacobucci
Journal: BMJ (2018)

An absence of public health resourcing in London is leaving the capital vulnerable to serious infectious disease like avian flu or Ebola, the BMA has warned.

The BMA’s London regional council chair Gary Marlowe has written to the mayor of London Sadiq Khan to warn that London’s capacity to deal with an emergency outbreak has been reduced despite “the clear and present danger” posed.

Specifically, the …
EAACI position paper on how to classify cutaneous manifestations of drug hypersensitivity
Authors: Knut Brockow, Michael R. Ardern‐Jones, Maja Mockenhaupt, Werner Aberer, Annick Barbaud, Jean‐Christoph Caubet, Radoslaw Spiewak, María José Torres, Charlotte G. Mortz
Journal: Allergy (2018)

Abstract Drug hypersensitivity reactions ( DHR s) are common, and the skin is by far the most frequently involved organ with a broad spectrum of reaction types. The diagnosis of cutaneous DHR s ( CDHR ) may be difficult because of multiple differential diagnoses. A correct classification is important for the correct diagnosis and management. With these guidelines, we aim to give precise definitions and provide the background needed for doctors to correctly classify CDHR .
Combination chemotherapy with consecutive low-dose cisplatin with ifosfamide and epirubicin (CLD-IEP) in uterine sarcoma
Authors: F. Murakami, N. Ogawa, M. Yamada, S. Sakurai, T. Ishiya, K. Katase, K. Hasumi, Y. Shimizu
Journal: Journal of Clinical Oncology (2007)

10057 Background: To evaluate the efficacy and toxicity of CLD-IEP for patients (pts) with sarcoma uteri. Methods: Eligible criteria were: a histologic proof of advanced or recurrent sarcoma uteri; measurable lesions; age between 18 and 80 yrs; WHO PS 0–3; WBC = 3,000/μL; platelet count = 100,000/μL; hemoglobin level = 9 g/dL; adequate liver function; C-Cr = 40 mL/min; no lung, heart, or brain disease; no previous neoplastic disease; no prior chemotherapy; and informed consent. The CLD-IEP regimen was ifosfamide 700 mg/m 2 infused over 2 hrs days 1 through 3; epirubicin 50 mg/m 2 bolus day 5; and cisplatin 15 mg/m 2 infused over 4 hrs days 1 through 5. The treatment was repeated at 4-week intervals. Results: To date, forty eligible pts (16 leiomyosarcoma [LMS], 4 endometrial stromal sarcoma, and 20 carcinosarcoma) were enrolled in this study and all pts were assessable for response, toxicity, and survival. The median age was 52 yrs (range, 28–77). Thirteen pts received CLD-IEP in the neoadjuvant setting. Nine pts had prior radiotherapy. After a median of 4 cycles (range, 2–13), we observed objective responses in 24 pts (60%), with 5 (13%) CRs and 19 (48%) PRs (95% CI, 42% to 78%, 4% to 22%, 30% to 66%, respectively). Of 16 pts with LMS, 1 CR and 7 PRs (1 pt with good PR surviving more than 48 months after the start of CLD-IEP) were observed. Median overall survival time (MOS) after the start of CLD-IEP for all 40 pts was 17 months (range, 3 to 62). MOS was 20.5 months in the responders versus 9 months in the non-responders (Log-rank, p=0.023). The median progression-free survival time of the responders was 10.5 months. NCI-CTC grade 3 or 4 leucopoenia, neutropenia, thrombocytopenia, and anemia occurred in 63%, 75%, 12%, and 18%, respectively. There was no significant nausea/vomiting, nephrotoxicity, or CNS toxicity. Conclusions: CLD-IEP regimen has significant to moderate anti-tumor activity with acceptable toxicity in pts with sarcoma uteri including LMS. No significant financial relationships to disclose.
Agreement Between Pulmonologists For The Diagnosis Of Interstitial Lung Disease: A Study Of 275 Pulmonologists From 54 Countries
Authors: S. L. F. Walsh, D. Hansell, K. R. Flaherty, M. Wilsher, R. Nusser, V. Poletti, F. J. Martinez, E. Bendstrup, K. K. Brown, H. Taniguchi, Y. Kondoh, B. Crestani, V. Cottin, D. Valeyre, H. Nunes, J. C. Grutters, L. Richeldi, T. M. Maher, C. Vancheri, M. Kokosi, C. J. Ryerson, K. A. Johannson, B. J. Ley, E. P. Judge, G. Margaritopoulos, M. Kreuter, J. Behr, A. Morais, M. Wijsenbeek, T. J. Corte, I. Glaspole, P. Spagnolo, S. Tomassetti, M. Molina-Molina, M. Selman, V. Kouranos, W. A. Wuyts, M. Jones, A. U. Wells
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Associations of Observed Performance Monitoring During Preschool With Obsessive-Compulsive Disorder and Anterior Cingulate Cortex Volume Over 12 Years
Authors: Kirsten E. Gilbert, Margot E. Barclay, Rebecca Tillman, Deanna M. Barch, Joan L. Luby
Journal: JAMA Psychiatry (2018)

Monitoring one's performance is necessary for learning and adaptive behavior; however, heightened performance monitoring is a purported endophenotype of obsessive-compulsive disorder (OCD). The anterior cingulate cortex (ACC), a brain region implicated in the pathogenesis of OCD, is associated with performance monitoring. Whether performance monitoring early in development is an identifiable risk factor for OCD and whether early childhood performance monitoring is associated with later alterations in ACC volume are unknown.To determine whether an observed indicator of heightened performance monitoring during the preschool age is associated with later onset of OCD and altered dorsal ACC (dACC) volume through adolescence.This longitudinal observational cohort study was performed at an academic medical center as part of the Preschool Depression Study. A sample of 292 children oversampled for depression from September 22, 2003, through May 12, 2005, completed a performance-based observational task during which they received persistent negative evaluation. Blind raters behaviorally coded child performance monitoring. During the next 12 years, children completed annual diagnostic assessments; 133 completed the final behavioral follow-up and 152 contributed 1 to 3 magnetic resonance imaging scans. Follow-up was completed on August 14, 2017.Onset of DSM-5 diagnosis of OCD from baseline to the final behavioral assessment and whole-brain-adjusted dACC volume at the 3 waves of scanning.Among the 292 preschool children who completed the baseline evaluation (51.4% boys; mean [SD] age, 4.5 [0.8] years), when controlling for demographic and clinical indicators, those who exhibited observed heightened performance monitoring were 2 times more likely to develop OCD (n = 35) during the next 12 years (odds ratio, 2.00; 95% CI, 1.06-3.78; P = .03). Multilevel modeling of dACC volume across the 3 scan waves (n = 152) demonstrated that heightened performance monitoring was associated with smaller right dACC volume (intercept estimate, -0.14; SE, 0.07; t = -2.17; P = .03).An ecologically valid indicator of performance monitoring in early childhood was associated with onset of OCD and smaller dACC volumes in later childhood and adolescence. Early childhood observed performance monitoring is a readily observed risk factor of OCD that can be identified in preschool-aged children.
Characteristics and Treatment of Chronic Chikungunya Virus: Comment on the Article by Chang et al
Authors: Shefali K. Sharma, M. B. Adarsh, Preksha Trivedi, Manod Reddy, Mini P. Singh, Varun Dhir, Shobha Sehgal, Sanjay Jain
Journal: Arthritis & Rheumatology (2018)
Early detection and treatment strategies for breast cancer in low-income and upper middle-income countries: a modelling study
Authors: Jeanette K Birnbaum, Catherine Duggan, Benjamin O Anderson, Ruth Etzioni
Journal: The Lancet Global Health (2018)

Poor breast cancer survival in low-income and middle-income countries (LMICs) can be attributed to advanced-stage presentation and poor access to systemic therapy. We aimed to estimate the outcomes of different early detection strategies in combination with systemic chemotherapy and endocrine therapy in LMICs.We adapted a microsimulation model to project outcomes of three early detection strategies alone or in combination with three systemic treatment programmes beyond standard of care (programme A): programme B was endocrine therapy for all oestrogen-receptor (ER)-positive cases; programme C was programme B plus chemotherapy for ER-negative cases; programme D was programme C plus chemotherapy for advanced ER-positive cases. The main outcomes were reductions in breast cancer-related mortality and lives saved per 100 000 women relative to the standard of care for women aged 30-49 years in a low-income setting (East Africa; using incidence data and life tables from Uganda and data on tumour characteristics from various East African countries) and for women aged 50-69 years in a middle-income setting (Colombia).In the East African setting, relative mortality reductions were 8-41%, corresponding to 23 (95% uncertainty interval -12 to 49) to 114 (80 to 138) lives saved per 100 000 women over 10 years. In Colombia, mortality reductions were 7-25%, corresponding to 32 (-29 to 70) to 105 (61 to 141) lives saved per 100 000 women over 10 years.The best projected outcomes were in settings where access to both early detection and adjuvant therapy is improved. Even in the absence of mammographic screening, improvements in detection can provide substantial benefit in settings where advanced-stage presentation is common.Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Cancer Center Support Grant of the US National Institutes of Health.
Finding the sweet spot via personalised Achilles tendon training: the future is within reach
Authors: Claudio Pizzolato, David G Lloyd, Ming H Zheng, Thor F Besier, Vickie B Shim, Steven J Obst, Richard Newsham-West, David J Saxby, Rod S Barrett
Journal: British Journal of Sports Medicine (2018)

Musculoskeletal tissues, including tendon, are sensitive to their mechanical environment, with both excessive and insufficient loading resulting in reduced tissue strength. Although further research is required to elucidate the specific loading conditions (ie, magnitude, duration, frequency and rate) that maximise tendon adaptation, in vitro 1 2 and in vivo 3–6 evidence indicates tendon has an optimal range or ‘sweet spot’7 within which mechanical loading promotes positive tissue adaptation or homeostasis, with either too much or too little loading being detrimental (figure 1). In vitro bioreactor studies of rabbit Achilles tendon have shown that continuous 8 hours/day for 6 days of 6% cyclic strain at 0.25 Hz maintains1 and promotes2 tendon health, but the same duration and frequency with strain magnitude of 3% and 9% disrupted the extracellular matrix. Tendons that were load-deprived for 12 days increased their expression of collagen of inferior material properties (ie, type III) and had diminished mechanical performance. Health of these load-deprived tendons, represented by increased expression of type I collagen, was restored following the same loading regime (6 days, 8 hours/day, magnitude 6%, 0.25 Hz). In vivo studies have also systematically modulated Achilles tendon training regime by varying strain magnitude,3 6 8 duration,6 rate6 and frequency.3 6 Training at a frequency of 0.17 Hz and strain magnitude of 6.5% resulted in superior …
Bevacizumab (BEV)-based therapy in the treatment of recurrent glioblastoma (GBM) in patients (PTS) treated at a Brazilian cancer center.
Authors: Rodrigo Ramella Munhoz, Maria Ignez Freitas Melro Braghiroli, Juliana Florinda De Mendonga Rego, Paulo Marcelo Hoff, Olavo Feher, Artur Katz
Journal: Journal of Clinical Oncology (2012)

e12513 Background: Temozolomide (TMZ) both concurrently and after radiation therapy constitutes the standard of care for newly diagnosed GBM PTS. BEV is FDA approved option for recurrent high-grade gliomas PTS based on the results phase II trials. Reports of the use of BEV in these setting have been limited to USA and European academic centers thus far. Methods: We conducted a cross sectional retrospective study of 39 consecutive PTS with histologically confirmed GBM that received BEV in the second or third line setting. The main objective of this analysis was to assess the efficacy and safety of BEV given “off protocol” in an unselected cohort of PTS treated at a Brazilian teaching hospital cancer center and to compare our results to those reported by North American and European academic centers. PTS received first-line treatment with TMZ plus radiotherapy and most received maintenance TMZ and received Bev-based therapy at the time of disease progression. Main endpoints were the evaluation of progression-free survival (PFS), overall survival (OS) and safety. Results: Between 2007 and 2011, 39 PTS with recurrent GBM that received BEV in second (92%) or third-line (8%) were identified. Seven PTS progressed during concomitant RT and TMZ, and 40 during or after TMZ maintenance. 72% were male; median age: 56 years (range 22-79). Most patients (89,7%) received BEV in combination with irinotecan, and the median number of cycles, regardless of combination, was 14. Reasons for BEV discontinuation were disease progression in 79,5% and toxicity in 4 patients. There was one treatment related death due to thrombocytopenia and bleeding. Twenty-four PTS (61,5%) achieved an objective response with BEV. Median PFS of the patients that received BEV in either second or third line was 7.5 months and median OS was 22.6 months. No bowel perforations or any unexpected toxicities occurred. Conclusions: This constitutes the first report of recurrent GBM PTS treated with Bev in the Southern Hemisphere. In this unselected “real life” cohort of PTS with recurrent GBM we have been able to reproduce and confirm the efficacy and safety of this agent used in the treatment of GBM in the second and third line setting.