tbuckley/cabot-search huggingface dataset:
Can We Engineer a Human Cardiac Patch for Therapy?
Authors: Jianyi Zhang, Wuqiang Zhu, Milica Radisic, Gordana Vunjak-Novakovic
Journal: Circulation Research (2018)

Some of the most significant leaps in the history of modern civilization-the development of article in China, the steam engine, which led to the European industrial revolution, and the era of computers-have occurred when science converged with engineering. Recently, the convergence of human pluripotent stem cell technology with biomaterials and bioengineering have launched a new medical innovation: functional human engineered tissue, which promises to revolutionize the treatment of failing organs including most critically, the heart. This compendium covers recent, state-of-the-art developments in the fields of cardiovascular tissue engineering, as well as the needs and challenges associated with the clinical use of these technologies. We have not attempted to provide an exhaustive review in stem cell biology and cardiac cell therapy; many other important and influential reports are certainly merit but already been discussed in several recent reviews. Our scope is limited to the engineered tissues that have been fabricated to repair or replace components of the heart (eg, valves, vessels, contractile tissue) that have been functionally compromised by diseases or developmental abnormalities. In particular, we have focused on using an engineered myocardial tissue to mitigate deficiencies in contractile function.
Abstract 17402: Cardiac Myosin Regulatory Light Chain Phosphorylation Regulates Inotropic Response Against Alpha1- Adrenergic Stimulation
Authors: Masaya Taniguchi, Itaru Goto, Ryuji Okamoto, Satoshi Fujita, Kaoru Dohi, Norikazu Yamada, Mashio Nakamura, Takeo Itoh, Masaaki Ito
Journal: Circulation (2013)

Background:  Phosphorylation of myosin regulatory light chain (MLC2) in cardiac muscle is indispensable for normal cardiac function and cardiac-specific myosin light chain kinase (cMLCK) plays a main role in maintaining the its phosphorylation level. Here, we identified the additional other isoform of cMLCK in various mouse strains. To elucidate the importance of MLC2 phosphorylation in cardiac performance, we examined the effects of MLC2 phosphorylation on developed tension, twitch tension parameters and the inotropic response against phenylephrine, alpha1-adrenergic receptor agonist, using the mice that never express the previously reported cMLCK in nature.   Methods and Results:  Using the antibodies against cMLCK and nanoLC-MS/MS analysis, cMLCK with the molecular mass of 61 kDa (cMLCK-2), in addition to the previously reported 86 kDa cMLCK, was revealed to be expressed in mice heart. Among various mouse strains, C57BL/6N expressed only cMLCK-2 due to the point mutation in the cMLCK gene,  mylk3 , though its closest relative strain, C57BL/6J, expressed both isoforms. The level of MLC2 phosphorylation in C57BL/6N ventricular muscle was significantly lower than that in C57BL/6J. Compared with C57BL/6J, basal developed tension of left ventricular papillary muscles was significantly small and time to peak tension as well as half relaxation time were significantly prolonged in C57BL/6N. Phenylephrine increased concentration-dependently contractile force without changing MLC2 phosphorylation level and C57BL/6J revealed more significant positive inotropic response than C57BL/6N. The increase in the MLC2 phosphorylation by calyculin A, an inhibitor of protein phosphatases 1 and 2A, led to the enhanced positive inotropic response in C57BL/6N but not in C57BL/6J. There was a significant positive correlation between positive inotropic response against phenylephrine and MLC2 phosphorylation level ranging from 15% to 30%.   Conclusion:  Our results suggest that there exists the other isoform of cMLCK in mice heart. In addition, the basal level of MLC2 phosphorylation regulates developed tension, twitch parameters and sensitivity against alpha1-adrenergic receptor stimulation.
Abstract 208: Excessive Autophagy Contributes to Microvascular Endothelial Dysfunction in Prehypertensive Spontaneously Hypertensive Rats
Authors: Qianqian Dong, Wenjuan Xing, Feifei Su, Feng Gao, Siwang Wang, Haifeng Zhang
Journal: Circulation Research (2017)

Autophagy exists in vascular endothelial cells, however, the exact role of autophagy in hypertensive-associated vascular endothelial dysfunction remains largely elusive. We assessed the hypothesis that autophagy is one of the mechanisms of endothelial dysfunction in normotensive spontaneously hypertensive rats (SHRs). Age-matched male SHRs and Wistar Kyoto rats (WKY) aged 4 weeks (young) and 12 weeks (adult) were randomized into 2 groups and treated daily for 2 weeks by a) gavage with vehicle alone (normal saline) or b) intraperitoneally injection of rapamycin (1 mg/kg/day), and the vascular function of their isolated aorta and mesenteric artery was assessed in vitro . Furthermore, human umbilical vein endothelial cells (HUVECs) were incubated serum-starved for 6 h to induce excessive cell autophagy, and then incubated with DMEM containing 10% FBS and a) treated with 10 nmol/L insulin-like growth factor 1 (IGF-1) for 12 h, b) treated with 100 nmol/L Rapamycin for 1 h for 37°C. Compared with WKY, young and adult SHRs showed endothelial dysfunction of the aorta and mesenteric artery, along with decreased phosphorylated (p)-Akt, p-mTOR, and autophagic marker protein p62 and increased LC3 II/I in microvascular but not aortic tissues. Treatment of young SHRs with the mTOR inhibitor rapamycin aggravated the endothelial autophagy and subsequent impaired endothelial function. Moreover, IGF-1 significantly activated Akt/mTOR signaling in HUVECs and reduced autophagic levels, while rapamycin inhibited p-mTOR and increased autophagic levels. In conclusion, mesenteric endothelial dysfunction in prehypertensive SHRs is at least partly attributable to excessive autophagy in vascular tissues, and is likely mediated by the underactive Akt/mTOR signaling pathway; however, autophagy appears not to be responsible for the macrovascular endothelial dysfunction.
Abstract 20129: T Wave Area is an Electrocardiographic Marker of Cardiac Events Following Left Cardiac Sympathetic Denervation
Authors: Alan Sugrue, Peter A Noseworthy, Ram K Rohatgi, Christopher V DeSimone, J. Martijn Bos, Bo Qiang, Vaclav Kremen, Christopher Scott, Yehu Sapir, Zachi Attiae, Peter Brady, Samuel J Asirvatham, Paul A Friedman, Michael J Ackerman
Journal: Circulation (2016)

Introduction: Long QT syndrome (LQTS) is a genetic channelopathy associated with a risk of sudden cardiac death (SCD). Left cardiac sympathetic denervation (LCSD) is one of the current treatment op...
Esophageal Cancer
Authors: Janet M. Torpy, Alison E. Burke, Richard M. Glass
Journal: JAMA (2010)

Esophageal CancerT he esophagus is a tube-like organ made up of a lining and surrounding smooth muscle.It brings food from the mouth to the stomach.As is true of any other body organ, cancer can develop in the esophagus.Esophageal cancer can be either squamous cell carcinoma (from the usual type of cells that line the esophagus) or adenocarcinoma (if the cells have experienced a change to gland-like tissue).Adenocarcinomas usually occur in persons who have gastroesophageal reflux disease (GERD), which can, if left untreated, change normal esophageal cells to gland-like adenomatous cells.This is called Barrett esophagus.The August 11, 2010, issue of JAMA includes an article reporting that bisphosphonate medications for osteoporosis are not associated with an increase in the risk of esophageal cancer. COMMON RISK FACTORS FOR ESOPHAGEAL CANCER
Lung Cancer Stigma across the Social Network: Patient and Caregiver Perspectives
Authors: Stefano Occhipinti, Jeff Dunn, Dianne L. O’Connell, Gail Garvey, Patricia C. Valery, David Ball, Kwun M. Fong, Shalini Vinod, Suzanne Chambers
Journal: Journal of Thoracic Oncology (2018)

To examine the personal experiences of people with lung cancer and their caregivers and how stigma is manifested throughout a patient's social network.A qualitative thematic analysis of interviews with 28 patients with lung cancer and their caregivers was conducted. Telephone interviews were conducted and transcribed verbatim. Data analysis was guided by contemporary stigma theory.Patients and caregivers reported feeling high levels of felt stigma and concomitant psychological distress in response to the diagnosis of lung cancer. Three overarching themes emerged: the nexus of lung cancer and smoking, moralization, and attacking the link between lung cancer and smoking. Stigma was inevitably linked to smoking, and this formed the hub around which the other themes were organized. Caregivers reported feeling invisible and noted a lack of support systems for families and caregivers. In addition, there was evidence that caregivers experienced stigma by association as members of the patients' close networks. Both groups responded ambivalently to stigmatizing antismoking advertisements.The qualitative analysis demonstrated the complex interplay of the social and personal domains in the experience and outcomes of stigma in lung cancer. There is a significant potential for caregivers of patients with lung cancer to experience exacerbations of psychosocial distress as a consequence of widely shared negative views about lung cancer and its prognosis. It remains for researchers and practitioners to incorporate such complexity in addressing stigma and psychosocial distress in both patients and caregivers.
ENDOSCOPIC CHOLEDOCHODUODENOSTOMY (ECDT) FOR PALLIATION OF AMPULLARY TUMORS
Authors: G Machado, G Haddad, B Washeck, H Novaes
Journal: Endoscopy (2018)

The insertion of stents through the papillary orifice for palliation of ampullary tumors in patients unfit for surgical treatment, may be technically difficult as those tumours often present with distortion of the papillary anatomy. On the other hand, endoscopic papillotomy bears a high risk of complications in such patients.
Induced Differentiation of U937 Cells by 1,25-dihydroxyvitamin D3 Involves Cell Cycle Arrest in G1 That Is Preceded by a Transient Proliferative Burst and an Increase in Cyclin Expression
Authors: Nynke Y. Rots, Antonio Iavarone, Virginia Bromleigh, Leonard P. Freedman
Journal: Blood (1999)
Childhood bereavement
Authors: R. Harrington
Journal: BMJ (1996)

benefit individual patients.24They need to be large enough to allow sufficient statistical power to answer the research questions posed.It is also known that only a small proportion of eligible patients are entered into such trials (for example, only 3-5% of patients with cancer in Britain are included in clinical trials4).Among the many reasons for this lack of accrual is a belief that multicentre trials do not officially recognise the considerable time and effort required by clinicians to identify suitable patients, obtain informed consent, and complete the necessary forms.Incentives to recruit patients into trials are required.We suggest that clinicians' vital contribution to randomised controlled trials should be acknowledged separately at the end of published papers.In large multicentre trials it is often not practical or desirable for all collaborating clinicians to be mentioned as authors of papers.Thus many people's efforts in recruiting patients to trials go unrewarded: they do not have publications to their name, and their research is denied the recognition that, since the publication of the Culyer report,' is now necessary to gain funding.Benefits could be gained if it became standard practice for all published papers to incorporate a list of clinicians who enrolled more than a (trial specific) number of patients into the trial.Not only would this acknowledge the important work of these clinicians in the trial but it would also provide evidence of their participation in research for academic assessment and for their curriculum vitae and provide kudos for the clinicians and their department.
Economic Analysis of a Noninvasive Molecular Pathologic Assay for Pigmented Skin Lesions
Authors: John Hornberger, Daniel M. Siegel
Journal: JAMA Dermatology (2018)

A recently described noninvasive gene expression test (the pigmented lesion assay [PLA]) with adhesive patch-based sampling has the potential to rule out melanoma and the need for surgical biopsy of pigmented lesions suggestive of melanoma with a negative predictive value of 99% compared with 83% for the histopathologic standard of care. The cost implications of using this molecular test vs visual assessment followed by biopsy and histopathologic assessment (VAH) have not been evaluated.To determine potential cost savings of PLA use vs the VAH pathway.This health economic analysis performed from a US payer perspective was based on consensus treatment guidelines and fee schedules from the Centers for Medicare & Medicaid Services. Data for model input were derived from routine use of the test in US dermatology practices and literature. Participants included patients with primary cutaneous pigmented lesions suggestive of melanoma. Data were analyzed from February 8 to December 1, 2017.The primary analysis consisted of the relative reduction in costs of diagnostic surgical procedures for PLA vs VAH management. Additional analyses included stage-related treatment costs associated with delays in diagnosis.In the cost analysis for this economic model, the relative reduction in surgical procedure costs (biopsy and subsequent excision), assuming $0 for the PLA to facilitate multiple comparison scenarios, was -$395 compared with VAH. The relative reduction in stage-related treatment costs associated with the PLA was -$433 compared with VAH, primarily associated with avoidance of delays due to false-negative diagnoses. Surveillance costs were reduced by -$119 with the PLA. The total cost of fully adjudicating a lesion suggestive of melanoma by VAH was $947. At a mean selling price reference point for PLA of $500, cost savings of $447 (47%) per lesion tested could be realized.The results of this analysis suggest that the PLA reduces cost and may improve the care of patients with primary pigmented skin lesions suggestive of melanoma.
Advances in managing COPD related to α<sub>1</sub>‐antitrypsin deficiency: An under‐recognized genetic disorder
Authors: Timothy J. Craig, Maria Paula Henao
Journal: Allergy (2018)

Abstract α 1 ‐Antitrypsin deficiency (AATD) predisposes individuals to chronic obstructive pulmonary disease (COPD) and liver disease. Despite being commonly described as rare, AATD is under‐recognized, with less than 10% of cases identified. The following is a comprehensive review of AATD, primarily for physicians who treat COPD or asthma, covering the genetics, epidemiology, clinical presentation, screening and diagnosis, and treatments of AATD. For patients presenting with liver and/or lung disease, screening and diagnostic tests are the only methods to determine whether the disease is related to AATD. Screening guidelines have been established by organizations such as the World Health Organization, European Respiratory Society, and American Thoracic Society. High‐risk groups, including individuals with COPD, nonresponsive asthma, bronchiectasis of unknown etiology, or unexplained liver disease, should be tested for AATD. Current treatment options include augmentation therapy with purified AAT for patients with deficient AAT levels and significant lung disease. Recent trial data suggest that lung tissue is preserved by augmentation therapy, and different dosing schedules are currently being investigated. Effective management of AATD and related diseases also includes aggressive avoidance of smoking and biomass burning, vaccinations, antibiotics, exercise, good diet, COPD medications, and serial assessment.
Enhanced delivery of liposomes to lung tumor through targeting interleukin-4 receptor on both tumor cells and tumor endothelial cells
Authors: Lianhua Chi, Moon-Hee Na, Hyun-Kyung Jung, Sri Murugan Poongkavithai Vadevoo, Cheong-Wun Kim, Guruprasath Padmanaban, Tae-In Park, Jae-Yong Park, Ilseon Hwang, Keon Uk Park, Frank Liang, Maggie Lu, Jiho Park, In-San Kim, Byung-Heon Lee
Journal: Journal of Controlled Release (2015)
Dendritic Tau in Alzheimer’s Disease
Authors: Arne Ittner, Lars M. Ittner
Journal: Neuron (2018)

The microtubule-associated protein tau and amyloid-β (Aβ) are key players in Alzheimer's disease (AD). Aβ and tau are linked in a molecular pathway at the post-synapse with tau-dependent synaptic dysfunction being a major pathomechanism in AD. Recent work on site-specific modification of dendritic and more specifically post-synaptic tau has revealed new endogenous functions of tau that limits synaptic Aβ toxicity. Thus, molecular studies opened a new perspective on tau, placing it at the center of neurotoxic and neuroprotective signaling at the post-synapse. Here, we review recent advances on tau in the dendritic compartments, with implications for understanding and treatment of AD and related neurological conditions.
Recurrent lower respiratory tract infections in children
Authors: Fernando Maria de Benedictis, Andrew Bush
Journal: BMJ (2018)

### What you need to know

Acute respiratory infections account for about a third of all paediatric consultations to primary care and 8-18% of acute hospital admissions in the UK.12 Children, especially preschool children, may have up to 6-10 viral colds a year.13 Parents often seek reassurance that all is well, or they may have concerns about a serious illness, sometimes prompted by the family history or a disturbing diagnosis in a friend’s child (see Patient’s perspective box). Sleep disturbance and the time carers may have to be away from work can lead to stress and impaired quality of life.

When consulting with families, distinguish children with recurrent self limiting or minor problems—the majority of cases—from those with a more serious underlying condition who may need investigation and treatment. Differentiate lower and upper respiratory tract infections, which may be difficult because symptoms and signs overlap and both may be present at the same time.34 This article presents a practical approach to diagnosis and management of the otherwise apparently healthy child with recurrent lower respiratory tract infections. Acute respiratory infections and the management of children with …
DESCRIPTIVE ANALYSIS OF 159 CONSECUTIVE CAPSULE ENDOSCOPIES AT A REFERRAL CENTER IN BUDAPEST
Authors: D Lippai, M Fazekas, R Krenacs, P Miheller, K Mullner, L Madacsy, Z Tulassay
Journal: Endoscopy (2018)

To evaluate characteristics of patients visiting a referral center for capsule endoscopy (CE) during 2014 – 2017.
Enhancement Strategies for Cardiac Regenerative Cell Therapy
Authors: Kathleen M. Broughton, Mark A. Sussman
Journal: Circulation Research (2018)

The idiom heart of the matter refers to the focal point within a topic and, with regard to health and longevity, the heart is truly pivotal for quality of life. Societal trends worldwide continue toward increased percent body fat and decreased physical activity with coincident increases in chronic diseases including cardiovascular disease as the top global cause of death along with insulin resistance, accelerated aging, cancer. Although long-term survival rates for cardiovascular disease patients are grim, intense research efforts continue to improve both prevention and treatment options. Pharmacological interventions remain the predominant interventional strategy for mitigating progression and managing symptoms, but cellular therapies have the potential to cure or even mediate remission of cardiovascular disease. Adult stem cells are the most studied cellular therapy in both preclinical and clinical investigation. This review will focus on the advanced therapeutic strategies to augment products and methods of delivery, which many think heralds the future of clinical investigations. Advanced preclinical strategies using adult stem cells are examined to promote synergism between preclinical and clinical research, streamline implementation, and improve this imminent matter of the heart.
MIDDLE GASTROINTESTINAL BLEEDING AS MANIFESTATION OF COMPLICATED COELIAC DISEASE IN A GLUTEN-FREE DIET RESPONDER: CASE REPORT
Authors: C Rusu, T Pop, O Mosteanu, Z Sparchez
Journal: Endoscopy (2018)

A 64-year-old male, with familial history of coeliac disease (daughter), recently diagnosed (in the past 2 months) with coeliac disease himself after an episode of diarrhea and bloating was referred to tertiary medical care for a history of 3 episodes of obscure upper gastrointestinal bleeding through hematemesis and melena in the past 7 months. Patient started the gluten-free diet immediately after being diagnosed with excellent compliance and clinical response. Baseline investigations revealed slight sideropenic anemia and an elevated erythrocyte sedimentation rate. Abdominal ultrasound revealed 8 mm mural thickening at the level of terminal ileum, with few lymph nodes around it measuring less than 6 mm. Upper gastrointestinal (GI) endoscopy showed typical aspect of coeliac disease: complete loss of duodenal folds with mosaic pattern. Histology confirmed coeliac disease Marsh-Oberhuber type 3a. Computed tomographic (CT) enterography was performed and showed the same mural thickening observed ultrasonographically situated at the level of aortic bifurcation. The lesion presented intense contrast enhancement in both arterial and venous phases. Radiologist opined for the colon appartenance of the lesion because of the presence of “haustra”. In the same day, lower GI endoscopy with ileoscopy of the last 10 cm of terminal ileum was performed and was normal. CT enterography reinterpretation along with ultrasound reevaluation concluded that the lesion was most probable situated at the level of jejunum. Therefore a spiral enteroscopy was performed which found a 5 – 6 cm length stenosis in the middle jejunum, with malignant features from where 5 biopsies were taken. Histologic examination was still in progress at the moment of abstract submission.
Impact of cystic fibrosis on birthweight: a population based study of children in Denmark and Wales
Authors: Daniela K Schlüter, Rowena Griffiths, Abdulfatah Adam, Ashley Akbari, Martin L Heaven, Shantini Paranjothy, Anne-Marie Nybo Andersen, Siobhán B Carr, Tania Pressler, Peter J Diggle, David Taylor-Robinson
Journal: Thorax (2018)

Background Poor growth during infancy and childhood is a characteristic feature of cystic fibrosis (CF). However, the impact of CF on intrauterine growth is unclear. We studied the effect of CF on birth weight in Denmark and Wales, and assessed whether any associations are due to differences in gestational age at birth. Methods We conducted national registry linkage studies in two countries, using data for 2.2 million singletons born in Denmark (between 1980 and 2010) and Wales (between 1998 and 2015). We used hospital inpatient and outpatient data to identify 852 children with CF. Using causal mediation methods, we estimated the direct and indirect (via gestational age) effect of CF on birth weight after adjustment for sex, parity and socioeconomic background. We tested the robustness of our results by adjusting for additional factors such as maternal smoking during pregnancy in subpopulations where these data were available. Results Babies with CF were more likely to be born preterm and with low birth weight than babies with no CF (12.7% vs 5% and 9.4% vs 5.8% preterm; 11.9% vs 4.2% and 11% vs 5.4% low birth weight in Denmark and Wales, respectively). Using causal mediation methods, the total effect of CF on birth weight was estimated to be −178.8 g (95% CI −225.43 to −134.47 g) in the Danish population and −210.08 g (95% CI −281.97 to −141.5 g) in the Welsh population. About 40% of this effect of CF on birth weight was mediated through gestational age. Conclusions CF significantly impacts on intrauterine growth and leads to lower birth weight in babies with CF, which is only partially explained by shorter gestation.