tbuckley/cabot-search huggingface dataset:
Discoidin domain receptor-1: A novel molecular switch regulating fibrocalcific response in vascular smooth muscle cells
Authors: J.B. Krohn, J.D. Hutcheson, E.O. Martinez-Martinez, C.V.C. Bouten, M.P. Bendeck, E. Aikawa
Journal: Circulation (2015)

Background: Extracellular vesicle (EV)-derived microcalcifications formed in collagen-poor fibrous caps contribute to plaque rupture. Collagen accumulation and calcification are major determinants of plaque stability, although the mechanisms linking fibrotic and calcific responses are unknown. The collagen receptor discoidin domain receptor-1 (DDR-1) regulates plaque calcification in vivo; however, its role in the release of calcifying EVs remains unclear. We hypothesize that DDR-1 regulates the processes of fibrosis and EV-induced calcification in atherosclerotic plaques. Methods and results: Smooth muscle cells (SMC) from the carotid arteries of wild type and DDR-1 knockout (DDR-1-/-) mice (n=5 per group) were cultured in control or calcifying media. At days 14 and 21, cells were harvested and EVs isolated for analysis. Compared to wild type cells, DDR-1-/- SMCs exhibited a 3.5-fold increase in EV release (p<0.001) as well as elevated EV calcifying potential determined by EV-bound alkaline phosphatase (ALP) activity (470.4+/-30.0 vs. 19.1+/-2.3 ng/well/mg protein). DDR-1-/- SMCs showed an increase in ALP activity (220.3+/-31.2 vs. 6.9+/-1.2 ng/well/mg protein), calcification measured by alizarin red S absorbance (3.56+/-0.11 vs. 0.10+/-0.0008), and collagen type I accumulation (p=0.04). Transforming growth factor-[beta] (TGF[beta]) signaling has been implicated in both fibrotic and calcific responses. DDR-1-/- cells released significantly more TGF[beta] in calcifying medium (253.4+/-12.4 vs. 167.2+/-8.8 pg/ml, p<0.001), suggesting a connection between DDR-1 and TGF[beta] signaling. A selective TGF[beta] receptor I inhibitor mitigated the osteogenic potential of the DDR-1-/- phenotype with a significant decrease in EV release, ALP activity in SMCs and EVs, extracellular matrix calcification and collagen production. Analysis of TGF[beta]-associated pathways in DDR-1-/- SMCs revealed significantly increased p38 phosphorylation while phosphorylated Smad3 and JNK were inhibited.
More on Single-Beat Estimation of Right Ventriculoarterial Coupling in Pulmonary Arterial Hypertension
Authors: Khodr Tello, Manuel J. Richter, Jens Axmann, Martin Buhmann, Werner Seeger, Robert Naeije, Hossein Ardeschir Ghofrani, Henning Gall
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Even a $13 meal paid by pharma increases doctors’ opioid prescribing, study finds
Authors: Owen Dyer
Journal: BMJ (2018)

Even a single modest meal bought for a doctor by an opioid manufacturer’s sales representative—a common practice in the US—is associated with slightly increased opioid prescribing by that physician in the next year, new research shows.

Overall US opioid prescriptions have finally begun to decline after 15 years of rapid growth, but in the subset of doctors who had recently taken money or gifts from the industry prescriptions were still rising, the study found.

“I think if you were to speak to all these doctors, the vast majority would tell you, and sincerely believe, that this meal or speaking engagement they participated …
Premature Cardiac Disease and Death After Preterm Preeclampsia in Women Whose Infant Was Small for Gestational Age
Authors: Lionel Carbillon
Journal: JAMA Cardiology (2018)

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Abstract 18251: Differential DNA Methylation in Coronary Artery Restenosis After Angioplasty
Authors: Fernando Lanas, Jenny Ruedlinger, Nicolas Saavedra, Braulio Bobadilla, Marcelo Potthoff, Luis Perez, Luis Salazar
Journal: Circulation (2016)

Introduction: Coronary artery in-stent restenosis (ISR) occurs in 20 to 30% of those who receive bare metal stents and 5 to 10% with drug eluted stents. Since known clinical and genetic risk factor...
Harry Antoniades: researcher who saw liver disease as “a burning problem”
Authors: Penny Warren
Journal: BMJ (2018)

Credit: Rebecca Bowen

For Harry Antoniades, a doctor with exceptional ability and drive, liver disease was “a burning problem.” He took a “bench to bedside” approach to it, working tirelessly to research its mechanisms in the laboratory and translate his findings into better patient care. In a career that was all too short, he managed to make important discoveries about the cellular and molecular mechanisms of the liver. He set in train vital research that will be carried forward by his team.

Antoniades was born in London on 15 June 1974. His father—also a doctor—was Greek, and his mother was British. When he was a toddler, the family relocated to Athens, where he grew up with his two sisters. As well as doing well at school, he enjoyed sport, excelling at running.

Family continued to be important to Antoniades, and he made trips back to …
Abstract 14641: Sleep Disturbance is Associated With Lower Quality of Life and Greater Depressive Symptoms in Adults With Congenital Heart Defects
Authors: Nancy McCabe, Wendy Book, Carolyn Reilly, Sandra Dunbar
Journal: Circulation (2016)

Introduction:  Poor sleep quality is common in cardiac populations and known to increase adverse physical and psychological outcomes, but little is known about sleep quality or its association with outcomes in adults with congenital heart defects (ACHD).   Hypothesis:  Greater sleep disturbance will be associated with greater depressive symptoms and lower quality of life (QOL) in persons with ACHD.   Methods:  A secondary analysis of an observational, self-care study in patients with moderate or severe ACHD (n=125) was conducted. Patients were recruited from a single ACHD center and demographic (age, gender, race, education, employment status, marital status) and clinical data (defect severity, NYHA Class, BMI, Obstructive Sleep Apnea (OSA)), depressive symptoms (PHQ-9), sleep disturbance (PROMIS-Sleep) and overall QOL (VAS scale) were collected by chart review and self-report. Analyses included bivariate correlations and logistic and linear regression.   Results:  Patients were mean age 35 years (range 20-68), 56% female, 82% Caucasian, 53% severe ACHD, 26% NYHA Class III/IV, 3% OSA. Sixty-eight (54%) patients reported sleep disturbance (PROMIS t score >50), including low sleep quality, difficulties falling asleep, general sleep problems, and poor sleep refreshment. Persons with sleep disturbance were more likely to be functional NYHA Class III/IV vs I/II (p   Conclusions:  Sleep disturbance was independently associated with greater depressive symptoms and lower QOL in persons with ACHD. Improving sleep quality may represent an important target for improving psychological and QOL outcomes in ACHD.
Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology
Authors: Supriya G. Mohile, William Dale, Mark R. Somerfield, Mara A. Schonberg, Cynthia M. Boyd, Peggy S. Burhenn, Beverly Canin, Harvey Jay Cohen, Holly M. Holmes, Judith O. Hopkins, Michelle C. Janelsins, Alok A. Khorana, Heidi D. Klepin, Stuart M. Lichtman, Karen M. Mustian, William P. Tew, Arti Hurria
Journal: Journal of Clinical Oncology (2018)

Purpose To provide guidance regarding the practical assessment and management of vulnerabilities in older patients undergoing chemotherapy. Methods An Expert Panel was convened to develop clinical practice guideline recommendations based on a systematic review of the medical literature. Results A total of 68 studies met eligibility criteria and form the evidentiary basis for the recommendations. Recommendations In patients ≥ 65 years receiving chemotherapy, geriatric assessment (GA) should be used to identify vulnerabilities that are not routinely captured in oncology assessments. Evidence supports, at a minimum, assessment of function, comorbidity, falls, depression, cognition, and nutrition. The Panel recommends instrumental activities of daily living to assess for function, a thorough history or validated tool to assess comorbidity, a single question for falls, the Geriatric Depression Scale to screen for depression, the Mini-Cog or the Blessed Orientation-Memory-Concentration test to screen for cognitive impairment, and an assessment of unintentional weight loss to evaluate nutrition. Either the CARG (Cancer and Aging Research Group) or CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) tools are recommended to obtain estimates of chemotherapy toxicity risk; the Geriatric-8 or Vulnerable Elders Survey-13 can help to predict mortality. Clinicians should use a validated tool listed at ePrognosis to estimate noncancer-based life expectancy ≥ 4 years. GA results should be applied to develop an integrated and individualized plan that informs cancer management and to identify nononcologic problems amenable to intervention. Collaborating with caregivers is essential to implementing GA-guided interventions. The Panel suggests that clinicians take into account GA results when recommending chemotherapy and that the information be provided to patients and caregivers to guide treatment decision making. Clinicians should implement targeted, GA-guided interventions to manage nononcologic problems. Additional information is available at www.asco.org/supportive-care-guidelines .
Reproducibility of pretreatment lymphocyte-to-monocyte ratio (LMR) in rectal cancer.
Authors: Cieszymierz Gawiński, Mariola Winiarek, Sebastian Rybski, Maciej Temnyk, Katarzyna Kokoszyńska, Lucjan Wyrwicz
Journal: Journal of Clinical Oncology (2018)

715 Background: Lymphocyte-to-monocyte ratio (LMR) is a strong prognostic factor in many cancers. Recently, in Polish-2 study it was demonstrated to have a predictive value for hypofractionated neoadjuvant radiotherapy in rectal cancer (WCGIC 2017). LMR &gt; 2.6 was associated with significant improvement of overall survival after short-course radiotherapy (5x5 Gy) and consolidating chemotherapy when compared to chemoradiotherapy (HR 0.36). To our knowledge this is the first observation on use of a predictive biomarker for hypofractionated radiotherapy. In this study we assessed the intra-patient variability of pre-treatment LMR in order to evaluate its reproducibility. Methods: Patients with rectal cancer treated in Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland between January 2013 and August 2017 were identified. In order to test reproducibility of the biomarker, only the patients with minimum two peripheral blood morphology tests within 5 weeks prior to any anti-cancer therapy were selected. Other inclusion criteria were locally advanced rectal cancer with no distant metastasis; no prior radiotherapy or chemotherapy. Patients with LMR &gt; 2.6 were identified as “LMR high”. Results: After pre-screening of 719 rectal cancer patients, 50 patients met the inclusion criteria. LMRs calculated at two time-points were correlated with the coefficient of 0.588 (p &lt; 0.05). 40% of assessments were “LMR high”. In 18% of patients the second test has not confirmed initial assignment to LMR class (95% CI 8.6%-31.4%). If LMR at the first time-point was in the range of 2.2-3.0 (+/- 0.4 from cut off), the chance for misclassification rose to 40% (95% CI 12.2%-73.8%), while outside of this range it dropped to 7.5% (95% CI 1.6%-20.4%). Conclusions: In our study LMR demonstrated significant intra-patient variability, espetially in patients with LMR outside of the indicated range (2.2-3.0). Further translational research is needed to identify the exact biological context of this biomarker in order to identify the molecular subtype of rectal cancer responding to hypofractionated radiotherapy.
Intestinal HIF-1α deletion exacerbates alcoholic liver disease by inducing intestinal dysbiosis and barrier dysfunction
Authors: Tuo Shao, Cuiqing Zhao, Fengyuan Li, Zelin Gu, Limimg Liu, Lihua Zhang, Yuhua Wang, Liqing He, Yunhuan Liu, Qi Liu, Yiping Chen, Hridgandh Donde, Rui Wang, Venkatakrishna R. Jala, Shirish Barve, Shao-Yu Chen, Xiang Zhang, Yongping Chen, Craig J. McClain, Wenke Feng
Journal: Journal of Hepatology (2018)
Higher Lung Cancer Incidence in Young Women Than Young Men in the United States
Authors: Ahmedin Jemal, Kimberly D. Miller, Jiemin Ma, Rebecca L. Siegel, Stacey A. Fedewa, Farhad Islami, Susan S. Devesa, Michael J. Thun
Journal: New England Journal of Medicine (2018)

Previous studies showed a higher incidence of lung cancer among young women than among young men in the United States. Whether this pattern has continued in contemporary birth cohorts and, if so, whether it can be fully explained by sex differences in smoking behaviors are unknown.We examined the nationwide population-based incidence of lung cancer according to sex, race or ethnic group, age group (30 to 34, 35 to 39, 40 to 44, 45 to 49, and 50 to 54 years), year of birth (1945 to 1980), and calendar period of diagnosis (1995-1999, 2000-2004, 2005-2009, and 2010-2014), and we calculated female-to-male incidence rate ratios. We also examined the prevalence of cigarette smoking, using data from the National Health Interview Survey from 1970 to 2016.Over the past two decades, the age-specific incidence of lung cancer has generally decreased among both men and women 30 to 54 years of age in all races and ethnic groups, but the declines among men have been steeper. Consequently, among non-Hispanic whites, the female-to-male incidence rate ratios increased, exceeding 1.0 in the age groups of 30 to 34, 35 to 39, 40 to 44, and 45 to 49 years. For example, the female-to-male incidence rate ratio among whites 40 to 44 years of age increased from 0.88 (95% confidence interval [CI], 0.84 to 0.92) during the 1995-1999 period to 1.17 (95% CI, 1.11 to 1.23) during the 2010-2014 period. The crossover in sex-specific rates occurred among non-Hispanic whites born since 1965. Sex-specific incidence rates converged among non-Hispanic blacks, Hispanics, and non-Hispanic Asians and Pacific Islanders but crossed over from a higher incidence among men to a higher incidence among women only among Hispanics. The prevalence of cigarette smoking among women born since 1965 has approached, but generally not exceeded, the prevalence among men.The patterns of historically higher incidence rates of lung cancer among men than among women have reversed among non-Hispanic whites and Hispanics born since the mid-1960s, and they are not fully explained by sex differences in smoking behaviors. Future studies are needed to identify reasons for the higher incidence of lung cancer among young women. (Funded by the American Cancer Society.).
Accountable care organisations: campaigners lose first legal fight over NHS rollout
Authors: Gareth Iacobucci
Journal: BMJ (2018)

A legal challenge to the proposed introduction of accountable care organisations (ACOs) in England has been defeated in the High Court.

Lawyers acting for 999 Call for the NHS, a grassroots campaign group, had argued that the NHS would be exceeding its legal powers by going ahead with its plans for ACOs.1 But, in the first of two separate legal challenges against the proposals,2 Mr Justice Kerr ruled at the High Court in Leeds that the contracting arrangements as proposed by NHS England were not unlawful.

The campaigners immediately said that they would appeal the …
Epigenomic-Guided Mass Cytometry Profiling Reveals Disease-Specific Features of Exhausted CD8 T Cells
Authors: Bertram Bengsch, Takuya Ohtani, Omar Khan, Manu Setty, Sasikanth Manne, Shaun O’Brien, Pier Federico Gherardini, Ramin Sedaghat Herati, Alexander C. Huang, Kyong-Mi Chang, Evan W. Newell, Niels Bovenschen, Dana Pe’er, Steven M. Albelda, E. John Wherry
Journal: Immunity (2018)
Synthesis and evaluation of cationic polymeric micelles as carriers of lumbrokinase for targeted thrombolysis
Authors: Yang Pan, Xiahui Wang, Zongning Yin
Journal: Asian Journal of Pharmaceutical Sciences (2018)

To achieve targeted thrombolysis, a targeted delivery system of lumbrokinase (LK) was constructed using RGDfk-conjugated hybrid micelles. Based on the specific affinity of RGDfk to glycoprotein complex of GPⅡb/Ⅲa expressed on the surface of membrane of activated platelet, LK loaded targeted micelles (LKTM) can be delivered to thrombus. The hybrid micelles were composed of polycaprolactone-block-poly (2-(dimethylamino) ethyl methacrylate) (PCL-PDMAEMA), methoxy polyethylene glycol-block- polycaprolactone (mPEG-PCL) and RGDfk conjugated polycaprolactone-block- polyethylene glycol (PCL-PEG-RGDfk). PCL-PDMAEMA was synthesized via ring open polymerization (ROP) and atom transfer radical polymerization (ATRP). PCL-PEG-RGDfk was synthesized via ROP and carbodiimide chemistry. The prepared LKTM was characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). Colloidal stability assay showed the prepared LKTM was stable. Biocompatibility assay was performed to determine the safe concentration range of polymer. The assay of fluorescent distribution in vivo demonstrated that LKTM can be efficiently delivered to thrombi in vivo. Thrombolysis in vivo indicated the thrombolytic potency of LKTM was optimal in all groups. Notably, the laboratory mice treated with LKTM exhibited a significantly shorter tail bleeding time compared to those treated with LK or LK-loaded micelles without RGDfk, which suggested that the targeted delivery of LK using RGDfk-conjugated hybrid micelles effectively reduced the bleeding risk.
The spatial correspondence and genetic influence of interhemispheric connectivity with white matter microstructure
Authors: Jeroen Mollink, Stephen M. Smith, Lloyd T. Elliott, Michiel Kleinnijenhuis, Marlies Hiemstra, Fidel Alfaro-Almagro, Jonathan Marchini, Anne-Marie van Cappellen van Walsum, Saad Jbabdi, Karla L. Miller
Journal: Nature Neuroscience (2019)
Anticoagulant trial to prevent recurrent stroke stops early because of risk of bleeding
Authors: Jacqui Wise
Journal: BMJ (2018)

A trial comparing rivaroxaban with aspirin for the prevention of recurrent stroke had to be stopped early because of a lack of benefit and a risk of bleeding associated with the anticoagulant.

The study,1 published in the New England Journal of Medicine , found that rivaroxaban was not superior to aspirin in preventing recurrent stroke after an initial embolic stroke of undetermined source and was associated with a …
ISOLATED TERMINAL ILEUM LESIONS SPOTTED DURING ROUTINE COLONOSCOPY
Authors: O Ilyés, I Iozsef, Z Péter, P Miheller, ÁV Patai
Journal: Endoscopy (2018)

Isolated Terminal Ileum Lesions (ITIL) can occasionally be observed during routine endoscopic examination of the lower gastrointestinal tract, but the clinical significance, associated factors and treatment are unclear. The aim of the study was to assess the incidence, endoscopic findings, clinical features and treatment of Isolated Terminal Ileum Lesions found during endoscopic examination.
Corticosteroid use endpoints in neuro-oncology: Response Assessment in Neuro-Oncology Working Group
Authors: Nils D Arvold, Terri S Armstrong, Katherine E Warren, Susan M Chang, Lisa M DeAngelis, Jaishri Blakeley, Marc C Chamberlain, Erin Dunbar, Herbert H Loong, David R Macdonald, David A Reardon, Michael A Vogelbaum, Ying Yuan, Michael Weller, Martin van den Bent, Patrick Y Wen
Journal: Neuro-Oncology (2018)

Corticosteroids are the mainstay of treatment for peritumor edema but are often associated with significant side effects. Therapies that can reduce corticosteroid use would potentially be of significant benefit to patients. However, currently there are no standardized endpoints evaluating corticosteroid use in neuro-oncology clinical trials.
Five-Year Suicidal Ideation Trajectories Among Women Receiving or Being Denied an Abortion
Authors: M. Antonia Biggs, Heather Gould, Rana E. Barar, Diana G. Foster
Journal: American Journal of Psychiatry (2018)

Objective: The aim of this study was to assess the effects of receiving compared with being denied an abortion on women's experiences of suicidal ideation over 5 years. Method: The authors recruited 956 women from 30 U.S. abortion facilities. Women were interviewed by telephone 1 week after their abortion visit, then every 6 months for 5 years. Women who received near-limit abortions were compared with women who were denied an abortion and carried their pregnancies to term (turnaway-birth group). Women completed the suicidal ideation items on the Brief Symptom Interview (BSI) and the Patient Health Questionnaire (PHQ-9). The Sheehan Suicidality Tracking Scale was used to assess imminent suicidality. Adjusted mixed-effects regression analyses accounting for clustering by site and individual were used to assess whether levels and trajectories of suicidality differed by group. Results: One week after abortion seeking, 1.9% of the near-limit group and 1.3% of the turnaway-birth group reported any suicidal ideation symptoms on the BSI. Over the 5-year study period, the proportion of women with any suicidal ideation symptoms on the BSI declined significantly to 0.25% for women in the near-limit group and nonsignificantly to 0.21% for those in the turnaway-birth group. In four out of 7,247 observations (0.06%), women reported being imminently suicidal. There was no statistically significant differential loss to follow-up by baseline report of suicidal ideation or history of depression or anxiety. There were no statistically significant group differences on any suicidal ideation outcome over the 5-year study period. Conclusions: Levels of suicidal ideation were similarly low between women who had abortions and women who were denied abortions. Policies requiring that women be warned that they are at increased risk of becoming suicidal if they choose abortion are not evidence based.