tbuckley/cabot-search huggingface dataset:
Abstract 15922: Fischer Rats Exhibit High Mortality in the Su5416 Model of Severe Pulmonary Arterial Hypertension Related to Failure of Right Ventricular Adaptation
Authors: Colin Suen, Baohua Jiang, Yupu Deng, Mohamad Taha, Ketul Chaudhary, Duncan J Stewart
Journal: Circulation (2015)

Introduction: Inhibition of VEGFR2 with SU5416 (SU) in combination with chronic hypoxia (CH), produces severe pulmonary arterial hypertension (PAH) in rats with complex arterial remodeling that closely resembles plexiform lesions typical of human PAH. Survival in severe PAH is related to the ability of the right ventricle (RV) to adapt to increased afterload. In this study, we explored the effect of genetic background on right ventricular adaptation and survival in the Methods: PAH was induced by a single subcutaneous injection of SU5416 (20mg/kg) in 6-week old Sprague-Dawley (SD, Harlan, USA) or Fischer rats (CDF, Charles River), followed by a 3-week exposure to CH (10% O2). RV structure and function was assessed by echocardiography (Vevo 2100, Visual Sonics) and cardiac MRI (Agilent 7.0T). Exercise capacity was evaluated at 4 weeks post-SU by treadmill testing. At end study (4 or 7 weeks post-SU), right ventricular systolic pressure (RVSP) was assessed by right heart catheterization. Results: SD and Fischer rats exhibited in similar elevations in RVSP (104± 13 vs 102 ±6 mmHg, respectively), number of occlusive pulmonary vascular lesions and RV hypertrophy (RV/LV+S) in response to SU/CH. However, Fischer rats exhibited markedly higher mortality, with only 27% surviving to 7 weeks compared with 100% survival in SD rats (p&lt;0.01), which was associated with significantly greater RV dilatation (RV/LV end diastolic diameter: 2.16 ± 0.24 vs. 1.19 ± 0.09 mm, p&lt;0.001) at 4 weeks post-SU (Figure 1). Additionally, RV capillary density (516 ± 55 vs 786 ± 38 capillaries/mm2) and exercise capacity (treadmill distance, 59 ± 29 vs 210 ± 52 m, p&lt;0.05) were also significantly reduced in Fischer vs SD SU/CH rats. Conclusions: These data suggest that the high mortality in Fischer compared to SD rats in the SU/CH model of severe PAH is related to a strain-dependent abnormality in RV adaptation at least in part due to lack of adequate microvascular angiogenesis in the hypertrophied RV.
Repeated thyroid function testing is unnecessary in previously euthyroid over 65s, study finds
Authors: Declan Murphy
Journal: BMJ (2018)

Routine thyroid function tests (TFT) in older people who have shown normal thyroid function in the previous five years is unnecessary unless their clinical circumstances change, a UK study has shown.1

The large, population based longitudinal investigation involving almost 3000 people aged over 65 showed high stability of thyroid function over a five year interval, especially in participants who were euthyroid (had normal TFT) at baseline.

“Reducing repeat thyroid function tests in older individuals is possible without conferring risk,” said the authors. “As well as reducing workload and patient inconvenience, following this …
Don’t get stuck in the mud: keep climbing for a better view of sport and exercise medicine
Authors: Hilde Moseby Berge
Journal: British Journal of Sports Medicine (2018)

Norway is well known for its spectacular fjords and snow-topped mountains, but reaching the summit can be very hard work. However, once you succeed, you are rewarded with fantastic views, something that we should also strive for in sport and exercise medicine, by improving the care we offer to our athletes. The Via Ferrata may be optimal for some, while gentler routes will suit others, but we should not get stuck in the mud while we strive to reach our ultimate goal.



This issue of BJSM was assembled by the Norwegian Sports Medicine and Sports Physiotherapy communities; the 2018 Annual Meeting will be held in the Unesco World Heritage City of Bergen. 



One year ago, BJSM launched a new series of educational editorials ( see page 1159 ), aimed at helping their readers to choose the best clinical pathways. The message was simply ‘methods matter’, as described in several papers in this issue. In Winters’ PhD Academy Award thesis ( see page 1213 ), two physicians made the same diagnosis independent of each other, while applying the same decision protocol for medial tibial stress syndrome. In contrast, the systematic review ( see page 1215 ) studying the effectiveness of physiotherapy, for pelvic and back pain after pregnancy, was unable to provide any conclusive answers, because all six studies used different methodology.

Sticking with the theme of evidence-based medicine, the study of rehabilitation of patients following ACL reconstruction ( see …
Genome organization and chromatin analysis identify transcriptional downregulation of insulin-like growth factor signaling as a hallmark of aging in developing B cells
Authors: Hashem Koohy, Daniel J. Bolland, Louise S. Matheson, Stefan Schoenfelder, Claudia Stellato, Andrew Dimond, Csilla Várnai, Peter Chovanec, Tamara Chessa, Jeremy Denizot, Raquel Manzano Garcia, Steven W. Wingett, Paula Freire-Pritchett, Takashi Nagano, Phillip Hawkins, Len Stephens, Sarah Elderkin, Mikhail Spivakov, Peter Fraser, Anne E. Corcoran, Patrick D. Varga-Weisz
Journal: Genome biology (2018)

Aging is characterized by loss of function of the adaptive immune system, but the underlying causes are poorly understood. To assess the molecular effects of aging on B cell development, we profiled gene expression and chromatin features genome-wide, including histone modifications and chromosome conformation, in bone marrow pro-B and pre-B cells from young and aged mice.Our analysis reveals that the expression levels of most genes are generally preserved in B cell precursors isolated from aged compared with young mice. Nonetheless, age-specific expression changes are observed at numerous genes, including microRNA encoding genes. Importantly, these changes are underpinned by multi-layered alterations in chromatin structure, including chromatin accessibility, histone modifications, long-range promoter interactions, and nuclear compartmentalization. Previous work has shown that differentiation is linked to changes in promoter-regulatory element interactions. We find that aging in B cell precursors is accompanied by rewiring of such interactions. We identify transcriptional downregulation of components of the insulin-like growth factor signaling pathway, in particular downregulation of Irs1 and upregulation of Let-7 microRNA expression, as a signature of the aged phenotype. These changes in expression are associated with specific alterations in H3K27me3 occupancy, suggesting that Polycomb-mediated repression plays a role in precursor B cell aging.Changes in chromatin and 3D genome organization play an important role in shaping the altered gene expression profile of aged precursor B cells. Components of the insulin-like growth factor signaling pathways are key targets of epigenetic regulation in aging in bone marrow B cell precursors.
Abstract 24: Graphene Oxide Containing Thermosensitive Hydrogel Improves the Survival of Transplanted Stem Cells in Ischemic Myocardium
Authors: Sekaran Saravanan, Ejlal Abu Al-Rub, Niketa Sareen, Glen Lester Sequiera, Meenal Moudgil, Sanjiv Dhingra
Journal: Circulation Research (2017)

Bone marrow derived mesenchymal stem cell (MSC) therapy has the potential to preserve cardiac function and prevent heart failure following a myocardial infarction (MI). However, in our recent studies, long term survival of transplanted stem cells was not detected, which was associated with deterioration of cardiac function. Therefore, strategies to enhance survival of transplanted cells would preserve the benefits of MSCs therapy for heart repair. Recently, graphene oxide (GO) nanosheets are being widely investigated for their ability to promote adherence and homing of transplanted MSCs to the extra cellular matrix in the heart. However, the presence of reactive oxygen functional groups (-OH, -COOH) in the structure of GO increases oxidative stress and activate apoptotic pathways in MSCs, which impairs the benefits of GO based biomaterials. Therefore, to nullify these side effects of GO, we synthesized a novel thermosensitive hydrogel by conjugating GO with chitosan (CS). Our Fourier transformed infrared spectrum (FTIR) analysis revealed an interaction between the oxygen functional groups of GO and amino (-NH2) groups of chitosan. Our data also demonstrate that CS masked the reactive functional groups of GO and prevented GO mediated ROS induction. This novel chitosan-graphene oxide (CS-GO) composite exhibited optimal porosity for cell conjugation and retention. Furthermore, this novel biomaterial was cyto-compatible as it exerted negligible toxicity to encapsulated MSCs. Upon exposure to hypoxic/ischemic environment, we observed a significant increase in apoptosis in MSCs as evidenced by an increase in the Bax/Bcl-xl ratio and caspase 3 activation. However, conjugation of MSCs to CS-GO polymer prevented hypoxia induced apoptosis. Therefore, coupling of GO with chitosan prevented GO mediated oxidative stress and downregulated hypoxia induced apoptosis of MSCs. Therefore, the outcome of this study will provide a novel delivery system for MSCs to the heart and improve their long term survival in the infarcted heart.
NHS plan to restrict funding is not based on high quality data
Authors: David Shewring, Jonathan Hobby, David Warwick, Tim Davis
Journal: BMJ (2018)

NHS England plans to restrict funding for 17 procedures that it considers unnecessary, to save money and eliminate unwarranted clinical variation.12 The policy is supposedly based on best clinical evidence and endorsed by the National Institute for Health and Care Excellence and the Academy of Medical Royal Colleges.

Carpal tunnel syndrome, Dupuytren disease, and trigger finger are common and have a substantial …
99mTc-Pertechnetate-SPECT/US Hybrid Imaging Enhances Diagnostic Certainty Compared With Conventional Thyroid Imaging With Scintigraphy and Ultrasound
Authors: Martin Freesmeyer, Thomas Winkens, Christian Kuehnel, Thomas Opfermann, Philipp Seifert
Journal: Clinical Nuclear Medicine (2018)

Abstract Evaluation of thyroid ultrasound and 99m Tc-pertechnetate scintigraphy side by side frequently produces ambiguous results regarding the correct assignment of anatomy and functionality of a nodule. We describe the usefulness of 99m Tc-pertechnetate-SPECT/US-fusion imaging. A 75-year-old woman was referred for exclusion of cold nodules. After conventional diagnostics (in vitro thyroid parameters, B mode–US, planar 99m Tc-pertechnetate-thyroid scintigraphy), a SPECT was performed using a conventional gamma camera. The SPECT data set was transferred to an ultrasound device (LOGIQ E9), and sensor-navigated 3D ultrasound was performed. Both data sets (SPECT/US) were fused in real time, revealing the exact functional state of multiple nodules.
Abstract P005: Aspirin Use and Dementia: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Aozhou Wu, A. R Sharrett, Rebecca F Gottesman, Melinda C Power, Alden L Gross, Thomas Mosley, Andreea M Rawlings, Andrea L Schneider, Richa Sharma, Josef Coresh
Journal: Circulation (2018)

Background: Aspirin may help to prevent dementia through its antiplatelet and anti-inflammatory effects, but findings from previous studies are mixed. Considering the length of the preclinical phase of dementia, early initiation of regular aspirin use may be more protective against dementia than later initiation. In this study, we explored the association of regular aspirin use initiated during and after midlife with the risk of dementia. Methods: Using data from 1996 to 2013 on 10,398 ARIC participants, we assessed the association of self-reported prior duration of regular aspirin use which was collected during 1996-1998 (as the baseline of this study) with incident dementia after the baseline. Dementia cases were identified based on: in-person dementia ascertainment from 2011 to 2013; the Telephone Interview for Cognitive Status (TICS) or informant interviews on dementia; and hospital discharge codes/death certificate code by surveillance through 2013. The relative hazards of dementia across categories of the duration of regular aspirin use prior to baseline (&lt;2 years, 2 to &lt;5 years, and ≥ 5 years) were compared to no regular use by Cox proportional hazard models. We adjusted for potential confounders, including demographic variables and major dementia risk factors at baseline. In sensitivity analyses, propensity score weighting was applied. Subgroup analyses were conducted by age, gender, race, APOE, and diabetes status. Results: Participants had a median age of 62 (IQR: 58, 67) at baseline. 55.8% (5,805 of 10,398) were female and 20.6% (2,147 of 10,398) were African American. Lower but non-significant relative hazards (HR) were observed among participants with regular aspirin use for &lt; 2 years (HR: 0.85; 95% CI: 0.69 to 1.04) and ≥ 5 years (HR: 0.87; 95% CI: 0.68 to 1.11), but not for the 2-5 year interval. With propensity score weighting, regular aspirin use &lt; 2 years achieved marginal significance (HR: 0.79; 95% CI: 0.63 to 0.99), while the effect of regular aspirin use ≥ 5 years changed towards null (HR: 1.04; 95%CI: 0.75 to 1.46). Without a prior hypothesis, an interaction was found for diabetes status (p = 0.016) with a significant protective association of ever regular aspirin use compared to no regular use among non-diabetic participants (HR: 0.82; 95%CI: 0.69 to 0.98). Conclusions: We found a non-significant protective association of regular aspirin use at late-middle life with onward incident dementia in a community-dwelling population. Data suggest persons with fewer comorbidities, specifically without diabetes, might be more susceptible to the preventive effect of aspirin use on dementia. Our results are subject to confounding by indication, suggesting the need for additional studies in populations which have different covariate structures than ARIC.
Clinical Implications and Challenges of Artificial Intelligence and Deep Learning
Authors: William W. Stead
Journal: JAMA (2018)

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A theory of how evolved psychology underpins attitudes towards societal economics must go beyond exchanges and averages
Authors: Jennifer Sheehy-Skeffington, Lotte Thomsen
Journal: Behavioral and Brain Sciences (2018)

Abstract We applaud Boyer &amp; Petersen for the advancement of an ultimate explanation of the dynamics of folk-economic beliefs and the political actions linked to them. To our mind, however, key inference systems regulating societal interaction and resource distribution evolved for more core relations than those of proportionate exchange, and situational factors are not the only constraints on how such systems produce economic beliefs
Genomic analysis of response to lactic acidosis in human cancers
Authors: Ling-Yu Chen Julia, Joe E. Lucas, Thies Schroeder, Seiichi Mori, Joseph Nevins, Mark Dewhirst, Mike West, Jen-Tsan Ashley Chi
Journal: Cancer Research (2008)

2054   The tumor microenvironment has a significant impact on tumor development. Two important determinants of this environment are hypoxia and lactic acidosis. We developed genome-scale gene expression studies aiming to dissect transcriptional responses of HMEC cells to lactic acidosis and hypoxia  in vitro , and explore how they are linked to tumor clinical phenotypes  in vivo . Statistical methods were applied to derive experimental signatures for these phenotypes and analyze their associations to heterogeneous sets of published breast cancer datasets. We find lactic acidosis elicits expression responses dominated by acidosis which are unrelated to hypoxia and it serves as an independent biomarker of good prognosis in tumor progression. Additionally, we identified an inverse relationship between the lactic acidosis response and Akt pathways and showed that lactic acidosis could inhibit Akt activation and glycolytic phenotypes of cancer cells. These observations suggest mechanisms to rationalize the association between lactic acidosis responses with favorable clinical outcomes in human cancers. This reciprocal information acquired from  in vitro  perturbations and  in vivo  clinical phenotypes via microarray led to novel findings of roles played by key characteristics of the tumor microenvironment and the distinction between physiological parameters and cellular responses.
Abstract 11414: Temporary Right Ventricular Mechanical Support in Addition to a Left Ventricular Assist Device: When is It Required and When is Its Removal Feasible?
Authors: Michael Dandel, Evgenij Potapov, Thomas Krabatsch, Beate Jurmann, Christoph Knosalla, Roland Hetzer
Journal: Circulation (2014)

Background: Right ventricular failure (RVF) before, during and after left ventricular assist device (LVAD) insertion is associated with high mortality. Thus, preoperative (preop) distinction between impaired RVs with and without the potential for recovery during RV afterload reduction by an LVAD is paramount. During biventricular support, RV recovery allowing RVAD removal can occur after unloading by a temporary device but preop prediction of recovery, its postoperative (postop) assessment and the timing of RVAD removal are challenging. We analyzed these issues to improve preop decision making. Methods: To assess the predictability of RV recovery during LVAD or LVAD+RVAD support allowing RVF free outcome without RVAD, prospectively gathered data on preop RV size, shape and function, tricuspid regurgitation and pulmonary hemodynamics were tested for relationship with postop RV function. Right heart catheterization and echo variables collected during short stops of the RV pump were used to test the predictability of weaning success from RV support. Results: Of 283 evaluated pts (preop RVEF ≤ 30%), 235 received an LVAD (group A) and 48 LVAD+RVAD (group B). We compared in group A the preop data from pts with and without postop RVF and in group B those from pts with and without RV recovery during biventricular support. We found less altered RV size and shape, higher velocity of RV systolic wall motion and myocardial shortening and higher systolic pressure gradients between RV and right atrium in pts with no RVF during LVAD support and also in those with RVAD-promoted RV recovery (p &lt; 0.01). Combined assessment of myocardial velocity of shortening and RV size and geometry in relation to RV load showed the highest predictive values (83-97%) for preop distinction between impaired RVs with and without the potential to remain free from RVF after LVAD insertion or the potential to recover during RVAD support, and also for postop distinction between unloading promoted RV recovery with and without the potential to remain stable after RVAD removal. Conclusions: Preoperative assessment of RV ability to improve during LVAD ± temporary RVAD support and prediction of weaning results before RVAD removal can be improved by evaluation of RV size, shape and function in relation to RV load.
Abstract 472: The mTOR-Dependent Translatome Adapts Early Changes in Gene Expression During Cardiac Growth
Authors: Eva Riechert, Shirin Doroudgar, Thanh Cao Ho, Brandon Malone, Jana Burghaus, Hugo A Katus, Christoph Dieterich, Mirko Völkers
Journal: Circulation Research (2017)

Introduction: The mTOR kinase links nutrient and growth factor signaling to cell growth by controlling mRNA translation, but the role of translationally controlled networks during cardiac stress remains unknown. We hypothesized that activation of mTOR controls translation of networks of mRNAs, independent from transcription, to rapidly adapt gene expression to physiologic and pathologic stress. We tested this hypothesis by monitoring the transcriptome and the translatome after pharmacologic and genetic inhibition of mTOR in cardiac myocytes. Methods and Results: To define the mTOR-dependent translatome, we performed ribosome profiling after pharmacologic mTOR inhibition by Torin1. We found 166 decreased and 199 unchanged mRNAs that we used for further analysis. Among the decreased mRNAs, 17% have a known TOP or TOP like motif in the 5’UTR, explaining why mTOR inhibition selectively suppresses their translation. Gene ontology analyses of Torin1-suppressed mRNAs showed enrichment for genes involved in translation and metabolism. P roline -r ich A KT s ubstrate of 40 kDa (Pras40) inhibits mTORC1 activity. In vivo, mTOR inhibition by overexpression of Pras40 blocked pathologic growth, and improved cardiac function after transverse aortic constriction (TAC). Conversely, in a cardiomyocyte-specific Pras40 knock-out mouse, heart function was reduced and growth response attenuated after TAC surgery. Similarly, physiological heart growth was inhibited after Pras40 deletion. Mechanistically and in line with the pharmacologic results, global translation rates were decreased after Pras40 depletion. Mass-spectrometric analysis identified ribonucleoproteins, ribosomal proteins and chaperones as Pras40 interaction partners, suggesting a direct function in the protein synthesis and folding machinery downstream of mTOR. Monitoring the translatome in vivo after Pras40 depletion using a ribosome tagging approach, followed by ribosome profiling, identified the mTOR-dependent translatome. Conclusions: mTOR-dependent translational control might represent a crucial way of controlling gene expression during stress in the myocardium. Once elucidated, mTOR-based therapies could be a powerful approach to prevent worsening of cardiac function.
Abstract 18502: Association Between Socioeconomic Status of Neighborhoods and the Provision of Bystander Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis
Authors: Tsung-Chien Lu, Yi-Che Lin, Ming-Ju Hsieh, Wen-Chu Chiang, Matthew H Ma
Journal: Circulation (2016)

Introduction: Early provision of bystander-initiated cardiopulmonary resuscitation (BCPR) is a vital determinant of survival for Out-of-hospital Cardiac Arrest (OHCA) but the BCPR rates remain unsa...
Coalitional rivalry may hurt in economic exchanges such as trade but help in war
Authors: Rose McDermott
Journal: Behavioral and Brain Sciences (2018)

Abstract Economic exchange constitutes the basis of many, but not all, aspects of human cooperation. The incentives overlap with, but remain distinct in important ways, from other fundamental aspects of cooperation, including the organization of collective violence for combat. The specific alignment of sometimes-conflicting goals helps inform the construction of political ideology.
Abstract 18508: Extubation Failure is Associated With Increased Mortality Following First Stage Single Ventricle Reconstruction
Authors: Thomas Scodellaro, Jane McKenzie, Yves d’Udekem, Warwick Butt, Siva Namachivayam
Journal: Circulation (2016)

Introduction: Extubation following first stage single ventricle reconstruction surgery presents a considerable challenge to the patient and clinician. We aimed to identify the incidence, risk facto...