tbuckley/cabot-search huggingface dataset:
Dementia And Physical Activity (DAPA) trial of moderate to high intensity exercise training for people with dementia: randomised controlled trial
Authors: Sarah E Lamb, Bart Sheehan, Nicky Atherton, Vivien Nichols, Helen Collins, Dipesh Mistry, Sukhdeep Dosanjh, Anne Marie Slowther, Iftekhar Khan, Stavros Petrou, Ranjit Lall
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To estimate the effect of a moderate to high intensity aerobic and strength exercise training programme on cognitive impairment and other outcomes in people with mild to moderate dementia. <h3>Design</h3> Multicentre, pragmatic, investigator masked, randomised controlled trial. <h3>Setting</h3> National Health Service primary care, community and memory services, dementia research registers, and voluntary sector providers in 15 English regions. <h3>Participants</h3> 494 people with dementia: 329 were assigned to an aerobic and strength exercise programme and 165 were assigned to usual care. Random allocation was 2:1 in favour of the exercise arm. <h3>Interventions</h3> Usual care plus four months of supervised exercise and support for ongoing physical activity, or usual care only. Interventions were delivered in community gym facilities and NHS premises. <h3>Main outcome measures</h3> The primary outcome was score on the Alzheimer’s disease assessment scale-cognitive subscale (ADAS-cog) at 12 months. Secondary outcomes included activities of daily living, neuropsychiatric symptoms, health related quality of life, and carer quality of life and burden. Physical fitness (including the six minute walk test) was measured in the exercise arm during the intervention. <h3>Results</h3> The average age of participants was 77 (SD 7.9) years and 301/494 (61%) were men. By 12 months the mean ADAS-cog score had increased to 25.2 (SD 12.3) in the exercise arm and 23.8 (SD 10.4) in the usual care arm (adjusted between group difference −1.4, 95% confidence interval −2.6 to −0.2, P=0.03). This indicates greater cognitive impairment in the exercise group, although the average difference is small and clinical relevance uncertain. No differences were found in secondary outcomes or preplanned subgroup analyses by dementia type (Alzheimer’s disease or other), severity of cognitive impairment, sex, and mobility. Compliance with exercise was good. Over 65% of participants (214/329) attended more than three quarters of scheduled sessions. Six minute walking distance improved over six weeks (mean change 18.1 m, 95% confidence interval 11.6 m to 24.6 m). <h3>Conclusion</h3> A moderate to high intensity aerobic and strength exercise training programme does not slow cognitive impairment in people with mild to moderate dementia. The exercise training programme improved physical fitness, but there were no noticeable improvements in other clinical outcomes. <h3>Trial registration</h3> Current Controlled Trials ISRCTN10416500.
Islet transplantation versus insulin therapy in patients with type 1 diabetes with severe hypoglycaemia or poorly controlled glycaemia after kidney transplantation (TRIMECO): a multicentre, randomised controlled trial
Authors: Sandrine Lablanche, Marie-Christine Vantyghem, Laurence Kessler, Anne Wojtusciszyn, Sophie Borot, Charles Thivolet, Sophie Girerd, Domenico Bosco, Jean-Luc Bosson, Cyrille Colin, Rachel Tetaz, Sophie Logerot, Julie Kerr-Conte, Eric Renard, Alfred Penfornis, Emmanuel Morelon, Fanny Buron, Kristina Skaare, Gwen Grguric, Coralie Camillo-Brault, Harald Egelhofer, Kanza Benomar, Lionel Badet, Thierry Berney, François Pattou, Pierre-Yves Benhamou, Paolo Malvezzi, Igor Tauveron, Béatrice Roche, Christian Noel, Luc Frimat, Bruno Guerci, Nadine Pernin, Anaick Moisan, Virginie Persoons, Rimed Ezzouaoui, Valery Gmyr, Frédéric Thony, Yvan Bricault, Mathieu Rodière, Christian Sengel, Michel Greget, Iulian Enescu, Christian Noel, Marc Hazzan, Robert Caiazzo, Fanelly Torres, Kristel Le Mapihan, Violetta Raverdy, Marie-Ange Pierredon, Pierre-Jean Valette, Arnaud Muller, Jean Champagnac, Lucy Chaillous, Jacques Dantal, Pierre Cattan, Jean-Pierre Riveline, François Moreau, Philippe Baltzinger, Thibault Bahoune
Journal: The Lancet Diabetes & Endocrinology (2018)
The Postinjury Inflammatory State and the Bone Marrow Response to Anemia
Authors: Tyler J. Loftus, Juan C. Mira, Elizabeth S. Miller, Kolenkode B. Kannan, Jessica M. Plazas, Daniel Delitto, Julie A. Stortz, Jennifer E. Hagen, Hari K. Parvataneni, Kalia K. Sadasivan, Scott C. Brakenridge, Frederick A. Moore, Lyle L. Moldawer, Philip A. Efron, Alicia M. Mohr
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: The pathophysiology of persistent injury-associated anemia is incompletely understood, and human data are sparse.Objectives: To characterize persistent injury-associated anemia among critically ill trauma patients with the hypothesis that severe trauma would be associated with neuroendocrine activation, erythropoietin dysfunction, iron dysregulation, and decreased erythropoiesis.Methods: A translational prospective observational cohort study comparing severely injured, blunt trauma patients who had operative fixation of a hip or femur fracture (n = 17) with elective hip repair patients (n = 22). Bone marrow and plasma obtained at the index operation were assessed for circulating catecholamines, systemic inflammation, erythropoietin, iron trafficking pathways, and erythroid progenitor growth. Bone marrow was also obtained from healthy donors from a commercial source (n = 8).Measurements and Main Results: During admission, trauma patients had a median of 625 ml operative blood loss and 5 units of red blood cell transfusions, and Hb decreased from 10.5 to 9.3 g/dl. Compared with hip repair, trauma patients had higher median plasma norepinephrine (21.9 vs. 8.9 ng/ml) and hepcidin (56.3 vs. 12.2 ng/ml) concentrations (both P < 0.05). Bone marrow erythropoietin and erythropoietin receptor expression were significantly increased among patients undergoing hip repair (23% and 14% increases, respectively; both P < 0.05), but not in trauma patients (3% and 5% increases, respectively), compared with healthy control subjects. Trauma patients had lower bone marrow transferrin receptor expression than did hip repair patients (57% decrease; P < 0.05). Erythroid progenitor growth was decreased in trauma patients (39.0 colonies per plate; P < 0.05) compared with those with hip repair (57.0 colonies per plate; P < 0.05 compared with healthy control subjects) and healthy control subjects (66.5 colonies per plate).Conclusions: Severe blunt trauma was associated with neuroendocrine activation, erythropoietin dysfunction, iron dysregulation, erythroid progenitor growth suppression, and persistent injury-associated anemia.Clinical trial registered with www.clinicaltrials.gov (NCT 02577731).
Abstract 12108: Long-term Increased Inpatient and Outpatient Visits Associated With Cardiovascular Events: A Large Real World Study
Authors: Kathleen M Fox, Li Wang, Ruben G Quek, Shravanthi R Gandra, Lu Li, Onur Baser
Journal: Circulation (2015)

Introduction: This study evaluated the burden to patients and the healthcare system associated with a new cardiovascular event (CVEs) up to 3 years after a new CVE among high-risk hyperlipidemia patients. Hypothesis: High-risk hyperlipidemia patients with new CVEs have long-term clinical burden. Methods: Using the IMS LifeLink PharMetrics Plus claims database, this retrospective cohort study included high CV risk hyperlipidemia patients with and without a new CVE between 01/01/2006 and 06/30/2012. CVEs included primary inpatient claims for myocardial infarction, unstable angina, ischemic stroke, transient ischemic attack, revascularization and heart failure. Patients were stratified into two CV risk cohorts: history of cardiovascular disease (CVD) and coronary heart disease risk equivalent (CHD RE) [See table for definitions]. Propensity score matching was applied to compare the burden among patients with and without a new CVE, from 1 month through 3 years post-CVE date. Results: Total 21,482 patients were included in the history of CVD and 181,228 in the CHD RE cohort. During the 31-365 days post-new CVE, the mean inpatient length of stay was significantly longer for patients with a new CVE than for those without (history of CVD: 6.61 vs. 2.06 days; CHD RE: 3.20 vs. 0.70 days, both p&lt;0.0001). This trend was sustained through 3 years post-new CVE for both cohorts. In both cohorts, significantly more inpatient, outpatient and pharmacy visits per patient per month were observed between patients with and without a new CVE during month 1 and years 1, 2 and 3 post new CVE (Table). Conclusions: High-risk hyperlipidemia patients with new CVEs had significantly higher burden of hospitalizations and healthcare visits compared to matched patients without new CVEs, evident in the 1st month and sustained through 3 years post-CVE. Interventions used to prevent the occurrence of CVEs may alleviate the long-term clinical burden among high-risk hyperlipidemia patients in the US.
The challenge of cerebral magnetic resonance imaging in neonates: A new method using mathematical morphology for the segmentation of structures including diffuse excessive high signal intensities.
Authors: Yongchao Xu, Baptiste Morel, Sonia Dahdouh, Élodie Puybareau, Alessio Virzì, Héléne Urien, Thierry Géraud, Catherine Adamsbaum, Isabelle Bloch
Journal: Medical Image Analysis (2018)
Winter pressure: England’s health regulator publishes tips to help emergency departments cope better next year
Authors: Jacqui Wise
Journal: BMJ (2018)

The Care Quality Commission has published several practical solutions that it says can help manage the ongoing trend of increased demand in emergency departments, but it urges systemwide action to make sure that hospitals are better prepared next winter.1

The independent regulator of health and social care in England says that action is needed now to tackle pressures on emergency departments and keep patients safe. As of April 2018, 4% of urgent and emergency services were rated inadequate, 46% required improvement overall, and 8% of services were rated inadequate for safety.

Ted Baker, chief inspector of hospitals at the Care Quality Commission, said, “We cannot accept that each winter will be worse than …
SHP2 is required for growth of KRAS-mutant non-small-cell lung cancer in vivo
Authors: Sara Mainardi, Antonio Mulero-Sánchez, Anirudh Prahallad, Giovanni Germano, Astrid Bosma, Paul Krimpenfort, Cor Lieftink, Jeffrey D. Steinberg, Niels de Wit, Samuel Gonçalves-Ribeiro, Ernest Nadal, Alberto Bardelli, Alberto Villanueva, Rene Bernards
Journal: Nature Medicine (2018)
Biomarker guided triage can reduce hospitalization rate in community acquired febrile urinary tract infection
Authors: Janneke Evelyne Stalenhoef, Cees van Nieuwkoop, Darius Cameron Wilson, Willize Elizabeth van der Starre, Nathalie Manon Delfos, Eliane Madeleine Sophie Leyten, Ted Koster, Hans Christiaan Ablij, Johannes(Jan) Willem van't Wout, Jaap Tamino van Dissel
Journal: Journal of Infection (2018)

ObjectivesFebrile urinary tract infections (fUTI) can often be treated safely with oral antimicrobials in an outpatient setting. However, a minority of patients develop complications that may progress into septic shock. An accurate assessment of disease severity upon emergency department (ED) presentation is therefore crucial in order to guide the most appropriate triage and treatment decisions.MethodsConsecutive patients were enrolled with presumptive fUTI across 7 EDs in the Netherlands. The biomarkers mid-regional proadrenomedullin (MR-proADM), procalcitonin (PCT), C-reactive protein (CRP), and a clinical score (PRACTICE), were compared in their ability to predict a clinically severe course of fUTI, initial hospital admission and subsequent readmission using area under the receiver operating characteristic (AUROC) curves.ResultsBiomarker concentrations were measured in 313 patients, with 259 (83%) hospitalized upon ED presentation, and 54 (17%) treated as outpatients. Of these outpatients, 12 (22%) were later hospitalized. MR-proADM had the highest diagnostic accuracy for predicting a complicated fUTI (AUROC [95% CI]: 0.86 [0.79–0.92]), followed by PCT (AUROC [95% CI]: 0.69 [0.58–0.80]). MR-proADM concentrations were unique in being significantly elevated in patients directly admitted and in outpatients requiring subsequent hospitalization, compared to those completing treatment at home. A virtual triage algorithm with an MR-proADM cut-off of 0.80 nmol/L resulted in a hospitalization rate of 66%, with only 2% secondary admissions.ConclusionMR-proADM could accurately predict a severe course in patients with fUTI, and identify greater patient numbers who could be safely managed as outpatients. An initial assessment on ED presentation may focus resources to patients with highest disease severities.
Abstract A38: Twist1-driven fatty pancreas formation facilitates pancreatitis and pancreatic ductal adenocarcinoma progression
Authors: Thien Ly Nguyen, Purba Singh, Parash Parajuli, Lianna Li, Celine Prunier, Santosh Kumar, Sailaja Eragmerdi, Seval Ozkan, Hao Me, Jussara do Carmo, John Hall, Azeddine Atfi
Journal: Cancer Research (2018)

Abstract Fatty pancreas or pancreatic steatosis has been associated with a variety of debilitating diseases, such as obesity, diabetes, pancreatitis, and pancreatic ductal adenocarcinoma (PDAC). Currently, neither the mechanisms underlying the pathogenesis of fatty pancreas nor the physiopathologic impacts of this disorder are well established. Serendipitously, we found that conditional overexpression of Twist1 in pancreatic progenitor cells in mice resulted in fatty pancreas development, leading to pancreatic insufficiency, severe hyperglycemia, and growth retardation. Molecular and genetic studies demonstrated that Twist1 drives fatty pancreas formation by selectively reprogramming acinar cells towards the adipocyte lineage albeit without affecting islet or ductal cell fate. Moreover, loss-of-function genetic experiments demonstrated that Twist1 plays a causative role in glucose tolerance, pancreatitis genesis, and PDAC progression. Finally, high levels of Twist1 expression correlate with fatty pancreas formation in patients with pancreatitis or PDAC, implicating Twist1 as a prognostic marker and possible target for attenuating several lethal diseases associated with fatty pancreas development. Citation Format: Thien Ly Nguyen, Purba Singh, Parash Parajuli, Lianna Li, Celine Prunier, Santosh Kumar, Sailaja Eragmerdi, Seval Ozkan, Hao Me, Jussara do Carmo, John Hall, Azeddine Atfi. Twist1-driven fatty pancreas formation facilitates pancreatitis and pancreatic ductal adenocarcinoma progression [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A38.
Abstract 10855: Impact of Race/Ethnicity, Sex, and Socio-Economic Status on the Risk for Heart Failure Readmission: The Importance of Context
Authors: Sonia Ponce, Diane Dodendorf, Deondrea Butler, Melissa Martinez, Bart Cox, Warren Laskey
Journal: Circulation (2015)

Background: Though Hispanics (H) have higher heart failure (HF)-related readmission rates compared to non-Hispanics (NH), their in-hospital mortality is reported as lower. Social determinants of health (e.g. educational attainment, annual income and geographic location) are associated with health outcomes regardless of ethnicity. The state of New Mexico has a large Hispanic community accounting for 47% of the population and is one of the poorest states in the country with low literacy levels. These factors make New Mexico a unique venue to assess health outcomes and the impact of ethnicity, sex, and social factors. Methods: We analyzed data from 1608 consecutive patients discharged from the University of New Mexico Hospital between 2010-2014 with a principle diagnosis of heart failure. We explored the associations between race/ethnicity, age, sex, level of poverty, education level, and distance from hospital and risk for 30 day readmission using univariable and multivariable statistical analysis. Results: Mean age on admission was 63.0 ± 14.1. Men represented 58.4% and 48.8% of the sample population were H. The overall 30 day readmission rate (30dRR) was 13.4%. 30dRR for H was 17.5% compared to 9.6% of NH (p&gt;0.00); for females, regardless of race/ethnicity, 30dRR was 16.7% compared to 10.9% for males (p=0.001). All selected socioeconomic variables were significantly associated with 30dRR on univariable analysis. However, on multivariable analysis only H ethnicity, sex, poverty level and distance from hospital were associated with readmission. Poverty level was strongly associated with higher 30dRR (OR 2.8; 95% CI 1.58-5.19; p&gt;0.001). Living furthest from hospital was associated with lower readmission rate (OR 0.5; 95% CI 0.3-0.8; p&gt;0.007). The rates of clinical characteristics (e.g., diabetes, hypertension, etc.) were similar between groups and did not associate with 30dRR. Conclusion: In this unique, less ethnically and socio-economically diverse environment where poverty rates are high and education attainment is low, Hispanic ethnicity, female sex, and living in poverty is associated with higher risk for 30dRR in patients with HF.
Is all morality or just prosociality externalized?
Authors: Michael J. Poulin
Journal: Behavioral and Brain Sciences (2018)

Abstract It is more likely that externalized morality that facilitated cooperation (externalized prosociality) was selected for versus other types of moral impulses. Recent research suggests that those other moral impulses may actually be at root prosocial, in that judgments about them are indirectly about avoidance of harm. Externalized prosociality may help explain why prosocial behavior benefits individuals.
Abstract 19345: A Novel Fibroblast Growth Factor-1 Ligand With Reduced Heparin Binding Protects the Heart Against Ischemia-Reperfusion Injury in the Presence of Heparin Co-Treatment
Authors: Chahua Huang, Andrew Beenken, Yang Liu, Moosa Mohammadi, Jo El J Schultz
Journal: Circulation (2016)

Introduction:  Fibroblast growth factor 1 (FGF1), a heparin/heparan sulfate (HS)-binding growth factor, is a potent cardioprotective agent against myocardial infarction (MI). The impact of heparin, the standard of care for MI patients entering the emergency room, on cardioprotective effects of FGF1 is unknown, however.   Hypothesis:  The working hypothesis to be tested is that reduction of heparin-binding of FGF1 will enhance targeting to the heart and the cardioprotective efficacy of this newly engineered ligand.   Methods:  To address this, a rat model of MI was employed to compare the cardioprotective potentials of native FGF1 and an engineered FGF1 (FGF1 ΔHBS ) with reduced heparin-binding affinity when given at the onset of reperfusion in the absence or presence of heparin. Hemodynamic parameters were measured by intracardiac catheter. Infarct size was determined by TTC staining. Blood clotting, FGF receptor (FGFR) activation and signaling as well as FGF biodistribution were also evaluated.   Results:  Native FGF1 and FGF1 ΔHBS  did not influence the anticoagulant property of heparin. Treatment with heparin alone or native FGF1 significantly reduced the infarct size compared to saline (46±9% heparin, 35±9% native FGF1 versus 58±5% saline; p ΔHBS  markedly reduced infarct size (22±6%) compared to native FGF1 (p ΔHBS ). Heparin reduced the biodistribution of native FGF1, but not FGF1 ΔHBS , to the left ventricle. Finally, both native FGF1 and FGF1 ΔHBS  bound and triggered FGFR1-induced downstream activation of ERK1/2 (p   Conclusions:  These findings demonstrate that modification of the heparin-binding region of FGF1 significantly improves the cardioprotective efficacy, even in the presence of heparin, identifying a novel FGF ligand available for therapeutic use in ischemic heart disease.
<i>STK11/LKB1</i> Mutations and PD-1 Inhibitor Resistance in <i>KRAS</i>-Mutant Lung Adenocarcinoma
Authors: Ferdinandos Skoulidis, Michael E. Goldberg, Danielle M. Greenawalt, Matthew D. Hellmann, Mark M. Awad, Justin F. Gainor, Alexa B. Schrock, Ryan J. Hartmaier, Sally E. Trabucco, Laurie Gay, Siraj M. Ali, Julia A. Elvin, Gaurav Singal, Jeffrey S. Ross, David Fabrizio, Peter M. Szabo, Han Chang, Ariella Sasson, Sujaya Srinivasan, Stefan Kirov, Joseph Szustakowski, Patrik Vitazka, Robin Edwards, Jose A. Bufill, Neelesh Sharma, Sai-Hong I. Ou, Nir Peled, David R. Spigel, Hira Rizvi, Elizabeth Jimenez Aguilar, Brett W. Carter, Jeremy Erasmus, Darragh F. Halpenny, Andrew J. Plodkowski, Niamh M. Long, Mizuki Nishino, Warren L. Denning, Ana Galan-Cobo, Haifa Hamdi, Taghreed Hirz, Pan Tong, Jing Wang, Jaime Rodriguez-Canales, Pamela A. Villalobos, Edwin R. Parra, Neda Kalhor, Lynette M. Sholl, Jennifer L. Sauter, Achim A. Jungbluth, Mari Mino-Kenudson, Roxana Azimi, Yasir Y. Elamin, Jianjun Zhang, Giulia C. Leonardi, Fei Jiang, Kwok-Kin Wong, J. Jack Lee, Vassiliki A. Papadimitrakopoulou, Ignacio I. Wistuba, Vincent A. Miller, Garrett M. Frampton, Jedd D. Wolchok, Alice T. Shaw, Pasi A. Jänne, Philip J. Stephens, Charles M. Rudin, William J. Geese, Lee A. Albacker, John V. Heymach
Journal: Cancer Discovery (2018)

Abstract KRAS is the most common oncogenic driver in lung adenocarcinoma (LUAC). We previously reported that STK11/LKB1 (KL) or TP53 (KP) comutations define distinct subgroups of KRAS-mutant LUAC. Here, we examine the efficacy of PD-1 inhibitors in these subgroups. Objective response rates to PD-1 blockade differed significantly among KL (7.4%), KP (35.7%), and K-only (28.6%) subgroups (P &amp;lt; 0.001) in the Stand Up To Cancer (SU2C) cohort (174 patients) with KRAS-mutant LUAC and in patients treated with nivolumab in the CheckMate-057 phase III trial (0% vs. 57.1% vs. 18.2%; P = 0.047). In the SU2C cohort, KL LUAC exhibited shorter progression-free (P &amp;lt; 0.001) and overall (P = 0.0015) survival compared with KRASMUT;STK11/LKB1WT LUAC. Among 924 LUACs, STK11/LKB1 alterations were the only marker significantly associated with PD-L1 negativity in TMBIntermediate/High LUAC. The impact of STK11/LKB1 alterations on clinical outcomes with PD-1/PD-L1 inhibitors extended to PD-L1–positive non–small cell lung cancer. In Kras-mutant murine LUAC models, Stk11/Lkb1 loss promoted PD-1/PD-L1 inhibitor resistance, suggesting a causal role. Our results identify STK11/LKB1 alterations as a major driver of primary resistance to PD-1 blockade in KRAS-mutant LUAC. Significance: This work identifies STK11/LKB1 alterations as the most prevalent genomic driver of primary resistance to PD-1 axis inhibitors in KRAS-mutant lung adenocarcinoma. Genomic profiling may enhance the predictive utility of PD-L1 expression and tumor mutation burden and facilitate establishment of personalized combination immunotherapy approaches for genomically defined LUAC subsets. Cancer Discov; 8(7); 822–35. ©2018 AACR. See related commentary by Etxeberria et al., p. 794. This article is highlighted in the In This Issue feature, p. 781