tbuckley/cabot-search huggingface dataset:
Gene expression signature of the ageing lung: breathing new life into COPD
Authors: Steven Booth, Tillie-Louise Hackett
Journal: Thorax (2018)

Due to consistently low birth rates and a higher life expectancy, countries within the European Union are transitioning to a much older population structure.1 The average number of older persons in the total population will increase significantly in the coming decade, as a large proportion of the post-war, baby-boom generation will reach retirement. Compared with generations prior, the ‘baby boomers’ were the most physically fit generation; however, they also grew up when smoking rates and exposure to secondhand smoke were at their peak.2

Tobacco use is a risk factor for six of the eight leading causes of death in the world including respiratory and cardiovascular diseases, stroke and cancer.2 Of these diseases, chronic obstructive pulmonary disease (COPD) is a major growing cause of morbidity and mortality3 with smoking and secondhand smoke exposure being the most important causative factors of the disease.3 In the European Union, the total direct costs of COPD account for 56% (€38.6 billion) of the total healthcare budget. As there is growing evidence that up to 50% of smokers will eventually develop COPD,4–6 the ageing ‘baby-boomer’ population will therefore have a significant effect on future healthcare demands.7

COPD is characterised by irreversible chronic airflow limitation that is caused by emphysematous destruction of lung elastic tissue and obstruction in the small airways due to occlusion of their lumen by inflammatory mucus exudates, narrowing and obliteration. In COPD, the airflow limitation measured by reduced forced expiratory volume in 1 s, progresses very slowly over time—potentially due to the high redundancy of small airway generations.8 9 Therefore, despite symptoms such as cough and phlegm being associated with susceptible smokers aged 20–44 years who will develop COPD, loss of lung function is …
Abstract 19477: Left Ventricular Function Improves in Heart Failure Patients Treated With Sacubitril-Valsartan
Authors: Hamed Nazzari, Michael Yeung, Aude Marceau, Michael Luong, Catherine Clark, Stephanie Ahuja, Jennifer Knoll, Mirka Koscal, Margot Davis, Sean Virani, Andrew Ignaszewski, Mustafa Toma
Journal: Circulation (2017)

Background: Sacubitril-valsartan has been shown to improve morbidity and mortality in heart failure patients with reduced left ventricular (LV) ejection fraction (EF). However, there is little data...
Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia
Authors: Nicola Gökbuget, Hervé Dombret, Massimiliano Bonifacio, Albrecht Reichle, Carlos Graux, Christoph Faul, Helmut Diedrich, Max S. Topp, Monika Brüggemann, Heinz-August Horst, Violaine Havelange, Julia Stieglmaier, Hendrik Wessels, Vincent Haddad, Jonathan E. Benjamin, Gerhard Zugmaier, Dirk Nagorsen, Ralf C. Bargou
Journal: Blood (2018)
Efficacy and safety of oxymetazoline cream 1.0% for treatment of persistent facial erythema associated with rosacea: Findings from the 52-week open label REVEAL trial
Authors: Zoe Diana Draelos, Michael H. Gold, Robert A. Weiss, Leslie Baumann, Steven K. Grekin, Deanne Mraz Robinson, Steven E. Kempers, Nancy Alvandi, Emily Weng, David R. Berk, Gurpreet Ahluwalia
Journal: Journal of the American Academy of Dermatology (2018)

Limited treatments are available for persistent erythema of rosacea.To examine the long-term safety and efficacy of oxymetazoline cream 1.0% in patients with rosacea with moderate-to-severe persistent erythema.Patients applied oxymetazoline once daily for 52 weeks. Safety assessments included treatment-emergent adverse events (TEAEs), skin blanching, inflammatory lesion counts, telangiectasia, disease severity, and rebound effect. Efficacy was assessed by the Clinician Erythema Assessment and Subject Self-Assessment composite score at 3 and 6 hours after the dose on day 1 and at weeks 4, 26, and 52.Among 440 patients, 8.2% reported treatment-related TEAEs; the most common were application-site dermatitis, paresthesia, pain, and pruritus. The rate of discontinuation due to adverse events (mostly application-site TEAEs) was 3.2%. No clinically meaningful changes were observed in skin blanching, inflammatory lesions, or telangiectasia. At week 52, 36.7%, and 43.4% of patients achieved a 2-grade or greater composite improvement from baseline in both Clinician Erythema Assessment and Subject Self-Assessment 3 and 6 hours after a dose, respectively. Less than 1% of patients experienced a rebound effect following treatment cessation.A vehicle-control group was not included.This long-term study demonstrated sustained safety, tolerability, and efficacy of oxymetazoline for moderate-to-severe persistent erythema of rosacea.
A Multicenter Study of the Validity and Reliability of Responses to Hand Cold Challenge as Measured by Laser Speckle Contrast Imaging and Thermography
Authors: Jack D. Wilkinson, Sarah A. Leggett, Elizabeth J. Marjanovic, Tonia L. Moore, John Allen, Marina E. Anderson, Jason Britton, Maya H. Buch, Francesco Del Galdo, Christopher P. Denton, Graham Dinsdale, Bridgett Griffiths, Frances Hall, Kevin Howell, Audrey MacDonald, Neil J. McHugh, Joanne B. Manning, John D. Pauling, Christopher Roberts, Jacqueline A. Shipley, Ariane L. Herrick, Andrea K. Murray
Journal: Arthritis & Rheumatology (2018)

Objective Reliable and objective outcome measures to facilitate clinical trials of novel treatments for systemic sclerosis ( SS c)–related Raynaud's phenomenon ( RP ) are badly needed. Laser speckle contrast imaging ( LSCI ) and thermography are noninvasive measures of perfusion that have shown excellent potential. This multicenter study was undertaken to determine the reliability and validity of a hand cold challenge protocol using LSCI , standard thermography, and low‐cost cell phone/mobile phone thermography (henceforth referred to as mobile thermography) in patients with SS c‐related RP . Methods Patients with RP secondary to SS c were recruited from 6 UK tertiary care centers. The patients underwent cold challenge on 2 consecutive days. Changes in cutaneous blood flow/skin temperature at each visit were imaged simultaneously using LSCI , standard thermography, and mobile thermography. Measurements included area under the curve ( AUC ) for reperfusion/rewarming and maximum blood flow rate/skin temperature after rewarming ( MAX ). Test–retest reliability was assessed using intraclass correlation coefficients ( ICC s). Estimated latent correlations (estimated from multilevel models, taking values between −1 and 1; denoted as rho values) were used to assess the convergent validity of LSCI and thermography. Results In total, 159 patients (77% with limited cutaneous SS c) were recruited (84% female, median age 63.3 years). LSCI and standard thermography both had substantial reliability, with ICC s for the reperfusion/rewarming AUC of 0.67 (95% confidence interval [95% CI ] 0.54, 0.76) and 0.68 (95% CI 0.58, 0.80), respectively, and ICC s for the MAX of 0.64 (95% CI 0.52, 0.75) and 0.72 (95% CI 0.64, 0.81), respectively. Very high latent correlations were present for the AUC s of LSCI and thermography (ρ = 0.94; 95% CI 0.87, 1.00) and for the AUC s of standard and mobile thermography (ρ = 0.98; 95% CI 0.94, 1.00). Conclusion This is the first multicenter study to examine the reliability and validity of cold challenge using LSCI and thermography in patients with SS c‐related RP . LSCI and thermography both demonstrated good potential as outcome measures. LSCI , standard thermography, and mobile thermography had very high convergent validity.
Mogamulizumab (Anti-CCR4) in HTLV-1–Associated Myelopathy
Authors: Tomoo Sato, Ariella L.G. Coler-Reilly, Naoko Yagishita, Natsumi Araya, Eisuke Inoue, Rie Furuta, Toshiki Watanabe, Kaoru Uchimaru, Masao Matsuoka, Naoki Matsumoto, Yasuhiro Hasegawa, Yoshihisa Yamano
Journal: New England Journal of Medicine (2018)

Human T-lymphotropic virus type 1 (HTLV-1) causes the debilitating neuroinflammatory disease HTLV-1–associated myelopathy–tropical spastic paraparesis (HAM–TSP) as well as adult T-cell leukemia–lymphoma (ATLL). In patients with HAM–TSP, HTLV-1 infects mainly CCR4+ T cells and induces functional changes, ultimately causing chronic spinal cord inflammation. We evaluated mogamulizumab, a humanized anti-CCR4 monoclonal antibody that targets infected cells, in patients with HAM–TSP.
Evaluation of the Effectiveness and Safety of Pixantrone for the Treatment of Multiply Relapsed or Refractory Aggressive Non Hodgkin B-Cell Lymphoma in an Ongoing International Registry
Authors: Pier Luigi Zinzani, Belén Navarro, Juan-Manuel Sancho, Begoña Soler, Silvina Grasso Cicala, Lorena Yapur, Mario Spione
Journal: Blood (2017)
Intraoperative Molecular Imaging in Lung Cancer: The State of the Art and the Future
Authors: Stephan Rogalla, Sebastiaan C.M. Joosten, Israt S. Alam, Sanjiv S. Gambhir, Ophir Vermesh
Journal: Molecular Therapy (2018)

Lung cancer is the deadliest malignant disease in the United States and has a median survival of only 5–11 months at advanced stages.1 However, for patients with stage I–IIIA cancers, minimally invasive surgery with curative intent plays a key role in treatment,2 and improving signal to noise in identifying diseased tissue is therefore critical in guiding resection. Non-targeted dyes, such as fluorescein (FITC) or indocyanine green (ICG), have long been administered pre-operatively to improve tumor contrast and have significantly improved surgical outcomes.
Association of β-Amyloid and Apolipoprotein E ε4 With Memory Decline in Preclinical Alzheimer Disease
Authors: Yen Ying Lim, Pawel Kalinowski, Robert H. Pietrzak, Simon M. Laws, Samantha C. Burnham, David Ames, Victor L. Villemagne, Christopher J. Fowler, Stephanie R. Rainey-Smith, Ralph N. Martins, Christopher C. Rowe, Colin L. Masters, Paul T. Maruff
Journal: JAMA Neurology (2018)

Older age, high levels of β-amyloid (Aβ), and the presence of the apolipoprotein E (APOE) ε4 allele are risk factors for Alzheimer disease (AD). However, the extent to which increasing age, Aβ, and ε4 are associated with memory decline remains unclear, and the age at which memory decline begins for Aβ-positive ε4 carriers and noncarriers has not been determined.To determine the association of age, Aβ level, and APOE ε4 with memory decline in a large group of cognitively healthy older adults.This longitudinal observational study included cognitively healthy older adults (age >60 years) enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study from March 31, 2006, through March 31, 2017; of 1583 individuals enrolled, 1136 refused or were excluded owing to other criteria (eg, having mild cognitive impairment or AD). Participants underwent Aβ imaging in research clinics in Perth and Melbourne and more than 72 months of follow-up (at 18-month intervals). The association of age with memory was fitted to a quadratic model. Age was treated as a continuous, time-dependent variable.β-Amyloid imaging using positron emission tomography, genotyping for APOE ɛ4, and longitudinal neuropsychological assessments of episodic memory during the 72-month follow-up.Episodic memory composite score.Of the 447 participants, 203 (45.4%) were men and 244 (54.6%) were women; mean (SD) age was 72.5 (6.6) years. Equal proportions of female participants were observed in each Aβ-ɛ4 group (24 of 51 Aβ-positive ε4 noncarriers [47.1%] ; 35 of 64 Aβ-negative ε4 carriers [54.7%]; 40 of 72 Aβ-positive ε4 carriers [55.6%]; and 145 of 260 Aβ-negative ε4 noncarriers [55.8%]). Adults with Aβ findings (mean [SD] age, 74.4 [6.8] years) were approximately 4 years older than those negative for Aβ (mean [SD] age, 69.8 [6.1] years). Memory decline diverged significantly from Aβ-negative ɛ4 noncarriers at an earlier age in Aβ-positive ɛ4 carriers (64.5 years) than in Aβ-positive ɛ4 noncarriers (76.5 years), such that by 85 years of age, Aβ-positive ε4 carriers performed approximately 1.5 SD units worse on the episodic memory composite than Aβ-negative ε4 noncarriers and approximately 0.8 SD units worse than Aβ-positive ε4 noncarriers. Memory performance of Aβ-negative ɛ4 carriers did not differ from that of the Aβ-negative ɛ4 noncarriers (estimate [SE], 0.001 [0.001]; t = 0.526; P = .77).Prior work has shown that Aβ and ε4 combine to influence memory decline in nondemented older adults. Results of this study indicate that increasing age may further exacerbate these effects. The estimates provided may be used to determine the risk of memory decline associated with Aβ and ε4 at each age.
Increased degradation of ATP is driven by memory regulatory T cells in kidney transplantation tolerance
Authors: Maxim Durand, Florian Dubois, Cécile Dejou, Eugénie Durand, Richard Danger, Mélanie Chesneau, Carole Brosseau, Pierrick Guerif, Jean-Paul Soulillou, Nicolas Degauque, Jean-François Eliaou, Magali Giral, Nathalie Bonnefoy, Sophie Brouard
Journal: Kidney International (2018)
Associations Between Serum Bone Biomarkers in Early Breast Cancer and Development of Bone Metastasis: Results From the AZURE (BIG01/04) Trial
Authors: Janet Brown, Emma Rathbone, Samantha Hinsley, Walter Gregory, Fatma Gossiel, Helen Marshall, Roger Burkinshaw, Helen Shulver, Hasina Thandar, Gianfilippo Bertelli, Keane Maccon, Angela Bowman, Andrew Hanby, Richard Bell, David Cameron, Robert Coleman
Journal: JNCI Journal of the National Cancer Institute (2017)

Adjuvant therapies can prevent/delay bone metastasis development in breast cancer. We investigated whether serum bone turnover markers in early disease have clinical utility in identifying patients with a high risk of developing bone metastasis.Markers of bone formation (N-terminal propeptide of type-1 collagen [P1NP]) and bone resorption (C-telopeptide of type-1 collagen [CTX], pyridinoline cross-linked carboxy-terminal telopeptide of type-1 collagen [1-CTP]) were measured in baseline (pretreatment blood samples from 872 patients from a large randomized trial of adjuvant zoledronic acid (AZURE-ISRCTN79831382) in early breast cancer. Cox proportional hazards regression and cumulative incidence functions (adjusted for factors having a statistically significant effect on outcome) were used to investigate prognostic and predictive associations between recurrence events, bone marker levels, and clinical variables. All statistical tests were two-sided.When considered as continuous variables (log transformed), P1NP, CTX, and 1-CTP were each prognostic for future bone recurrence at any time (P = .006, P = .009, P = .008, respectively). Harrell's c-indices were a P1NP of 0.57 (95% confidence interval [CI] = 0.51 to 0.63), CTX of 0.57 (95% CI = 0.51 to 0.62), and 1-CTP of 0.57 (95% CI = 0.52 to 0.63). In categorical analyses based on the normal range, high baseline P1NP (>70 ng/mL) and CTX (>0.299 ng/mL), but not 1-CTP (>4.2 ng/mL), were also prognostic for future bone recurrence (P = .03, P = .03, P = .10, respectively). None of the markers were prognostic for overall distant recurrence; that is, they were bone metastasis specific, and none of the markers were predictive of treatment benefit from zoledronic acid.Serum P1NP, CTX, and 1-CTP are clinically useful, easily measured markers that show good prognostic ability (though low-to-moderate discrimination) for bone-specific recurrence and are worthy of further study.
TGF-β/Smad signaling pathway positively up-regulates the differentiation of Interleukin-9-producing CD4 + T cells in human Echinococcus granulosus infection
Authors: Nannan Pang, Fengbo Zhang, Shaoyu Li, Yuejie Zhu, Chuntao Zhang, Mengting An, Hongying Wang, Wulamu Mamuti, Jianbing Ding, Haining Fan
Journal: Journal of Infection (2018)
Targeting p53-dependent stem cell loss for intestinal chemoprotection
Authors: Brian J. Leibowitz, Liheng Yang, Liang Wei, Monica E. Buchanan, Madani Rachid, Robert A. Parise, Jan H. Beumer, Julie L. Eiseman, Robert E. Schoen, Lin Zhang, Jian Yu
Journal: Science Translational Medicine (2018)

Targeting of p53- and PUMA-dependent apoptosis protects intestinal stem cells, but not cancer cells, against chemotherapy.
GP who sexually assaulted patients is jailed for 12 years
Authors: Clare Dyer
Journal: BMJ (2018)

A respected senior GP has been jailed for 12 years for sexually assaulting patients.

Jaswant Rathore was told by Judge Michael Challinor at Wolverhampton Crown Court that his personal and professional life had been turned into “a complete shipwreck.”

Rathore, 60, had practised as a GP in Dudley, West Midlands, for 30 years and had been the primary care lead for the Dudley clinical commissioning group.

He was found guilty of eight offences of sexual assault …
High-Dimensional Single-Cell Mapping of Central Nervous System Immune Cells Reveals Distinct Myeloid Subsets in Health, Aging, and Disease
Authors: Dunja Mrdjen, Anto Pavlovic, Felix J. Hartmann, Bettina Schreiner, Sebastian G. Utz, Brian P. Leung, Iva Lelios, Frank L. Heppner, Jonathan Kipnis, Doron Merkler, Melanie Greter, Burkhard Becher
Journal: Immunity (2018)
The seroprevalence rate and population genetic structure of human cystic echinococcosis in the Middle East: A systematic review and meta-analysis
Authors: Tahereh Mikaeili Galeh, Adel Spotin, Mahmoud Mahami-Oskouei, David Carmena, Mohammad Taghi Rahimi, Aleksandra Barac, Roghayeh Ghoyounchi, Reza Berahmat, Ehsan Ahmadpour
Journal: International Journal of Surgery (2018)
Large-scale Sequencing of Testicular Germ Cell Tumour (TGCT) Cases Excludes Major TGCT Predisposition Gene
Authors: Kevin Litchfield, Chey Loveday, Max Levy, Darshna Dudakia, Elizabeth Rapley, Jeremie Nsengimana, D. Tim Bishop, Alison Reid, Robert Huddart, Peter Broderick, Richard S. Houlston, Clare Turnbull
Journal: European Urology (2018)
Genital Chlamydia trachomatis infections in young adults – a school-based bio-behavioural study in urban areas, Poland, 2012 to 2015
Authors: Michal Czerwinski, Marta Niedzwiedzka-Stadnik, Anna Zielicka-Hardy, Anna Tomusiak, Malgorzata Sadkowska-Todys, Andrzej Zielinski, Magdalena Strus, Piotr Heczko, Magdalena Rosinska
Journal: Eurosurveillance (2018)

Context and AimOne of the most common sexually transmitted pathogens disproportionately affecting young people is Chlamydia trachomatis (CT). This study aimed to assess prevalence of CT among sexually active students (aged 18-19 years) in their final years of high school education in Warsaw and Krakow. Methods: The sample was selected from 61 clusters, each cluster representing one school. We described city, sex, type of school and their association with CT prevalence. To account for non-responders we applied inverse probability weighting. Results: Our study population consisted of 3,136 young adults eligible for CT screening, of whom 2,326 reported having had sexual intercourse within past 12 months. Of the 950 students who agreed to be tested, 39 were infected with CT. Weighted prevalence of CT was 3.9% (95% confidence interval (CI): 2.7-5.1); however, prevalence in the students in Warsaw (6.6%; 95% CI: 3.5-12.4) was six times higher (prevalence ratio (PR) = 5.9; 95% CI: 2.0-17.3) than in Krakow (1.1%; 95% CI: 0.5-2.6). In both settings, female students attending vocational-technical schools were most affected; the prevalence in this group was more than five times higher (PR = 5.2; 95% CI: 1.7-15.6) compared with female peers in high schools and more than three times higher (PR = 3.3; 95% CI: 1.0-10.7) compared with male peers attending vocational-technical schools. Conclusion: Our study suggested prevalence of CT infection among young people in Poland comparable with the European average, supporting implementation of a CT control programme as recommended in international guidelines.
Depression and anxiety symptoms in 17 teams of female football players including 10 German first league teams
Authors: Astrid Junge, Birgit Prinz
Journal: British Journal of Sports Medicine (2018)

Information on the prevalence of mental health problems of elite athletes is inconclusive, most probably due to methodological limitations, such as low response rates, heterogeneous samples.To evaluate the prevalence and risk factors of depression and anxiety symptoms in high-level female football players.Female football players of 10 German first league (Bundesliga) and 7 lower league teams were asked to answer a questionnaire on players' characteristics, the Center of Epidemiologic Studies Depression Scale (CES-D) and the Generalised Anxiety Disorder (GAD-7) scale.A total of 290 players (184 first and 106 lower league players) took part in the study. The CES-D score indicated mild to moderate symptoms of depression in 48 (16.6%) and severe symptoms in 41 (14.1%) players. The GAD-7 score indicated an at least moderate generalised anxiety disorder in 24 (8.3%) players. The prevalence of depression symptoms and generalised anxiety disorders was similar to the female general population of similar age. However, significantly more second league players reported symptoms of depression than first league players, and thus the prevalence of depression symptoms in second league players was higher than in the general population. Only a third of the 45 (15.7%) players who stated that they currently wanted or needed psychotherapeutic support received it.The prevalence of depression and generalised anxiety symptoms in elite football players is influenced by personal and sport-specific variables. It is important to raise awareness of athletes' mental health problems in coaches and team physicians, to reduce stigma and to provide low-threshold treatment.
The AJCC 8th Edition Staging System for Soft Tissue Sarcoma of the Extremities or Trunk: A Cohort Study of the SEER Database
Authors: Justin M. M. Cates
Journal: Journal of the National Comprehensive Cancer Network (2018)

Background: The AJCC recently published the 8th edition of its cancer staging system. Significant changes were made to the staging algorithm for soft tissue sarcoma (STS) of the extremities or trunk, including the addition of 2 additional T (size) classifications in lieu of tumor depth and grouping lymph node metastasis (LNM) with distant metastasis as stage IV disease. Whether these changes improve staging system performance is questionable. Patients and Methods: This retrospective cohort analysis of 21,396 adult patients with STS of the extremity or trunk in the SEER database compares the AJCC 8th edition staging system with the 7th edition and a newly proposed staging algorithm using a variety of statistical techniques. The effect of tumor size on disease-specific survival was assessed by flexible, nonlinear Cox proportional hazard regression using restricted cubic splines and fractional polynomials. Results: The slope of covariate-adjusted log hazards for sarcoma-specific survival decreases for tumors >8 cm in greatest dimension, limiting prognostic information contributed by the new T4 classification in the AJCC 8th edition. Anatomic depth independently provides significant prognostic information. LNM is not equivalent to distant, non-nodal metastasis. Based on these findings, an alternative staging system is proposed and demonstrated to outperform both AJCC staging schemes. The analyses presented also disclose no evidence of improved clinical performance of the 8th edition compared with the previous edition. Conclusions: The AJCC 8th edition staging system for STS is no better than the previous 7th edition. Instead, a proposed staging system based on histologic grade, tumor size, and anatomic depth shows significantly higher predictive accuracy, with higher model concordance than either AJCC staging system. Changes to existing staging systems should improve the performance of prognostic models. Until such improvements are documented, AJCC committees should refrain from modifying established staging schemes.