tbuckley/cabot-search huggingface dataset:
Debate over screening for gestational diabetes
Authors: M. Griffiths, F. Chiaffarino, F. Parazzini, A. Bortolotti, G. Benzi, J. Ray
Journal: BMJ (1998)

Editor—Jarrett and Soares et al present arguments respectively against and in favour of screening for gestational diabetes.1 Jarrett has been arguing objectively against gestational diabetes as a useful concept for many years.2 In contrast, many obstetricians and diabetologists have aggressively sought and treated this condition despite a lack of real evidence. Rather, they have worked on the assumption that there is a continuum from normal glucose tolerance through gestational diabetes to frank diabetes and that gestational diabetes must be a less severe form of diabetes. 

Screening for gestational diabetes presents a massive organisational and financial cost as well as a stressful burden to the women concerned. As Walkinshaw has shown, there is no evidence that attempts to control carbohydrate metabolism in women labelled as having gestational diabetes usefully alter perinatal outcome; rather, they lead to unnecessary interference.3 Had either Jarrett or Soares et al referred to Walkinshaw’s systematic review then one of the three arguments of Soares et al for screening could have immediately been dismissed as lacking in supportive evidence. Their other two arguments are no more certain: that the presence of gestational diabetes predicts an increased risk of maturity onset diabetes in later life, and that management of carbohydrate metabolism in the mother may prevent the child from developing long term medical problems as a result of an adverse intrauterine environment. 

Sufficient evidence probably exists to support the case that a degree of glucose intolerance predicts an increased risk of frank diabetes in later life. What is less clear is whether, as a result of subjects at increased risk being identified, any intervention can alter disease progression. Surely if there were such evidence, confining screening for such glucose intolerance solely to women who happen to be pregnant would be massively unfair—what about men with an increased risk of maturity onset diabetes, and childless women? 

The hypothesis regarding long term metabolic effects of an adverse (carbohydrate) intrauterine environment requires confirmation by prospective studies. In discussing this hypothesis Soares et al ignore the difference between frank diabetes and gestational diabetes once more. 

Until the relevance of gestational diabetes is known, screening for it should take place only in the context of good quality controlled trials. In the meantime we should continue to ensure good preconceptional and antenatal control of frank diabetes and aim to detect the few women who have frank diabetes not diagnosed before pregnancy. The benefits of treating such women have been shown by many authors.
Coping behavior of the rape victim
Authors: Ann Wolbert Burgess, L. L. Holmstrom
Journal: American Journal of Psychiatry (1976)

The coping behavior of rape victims can be analyzed in three distinct phases--the threat of attack, the attack itself, and the period immediately thereafter. The authors analyzed the reported coping behavior of 92 women diagnosed as having rape trauma. Most of the women used verbal, physical, or cognitive strategies when threatened, although 34 were physically or psychologically paralyzed. The actual rape prompted coping behaviors in all but 1 victim. Escaping the situation or the assailant is the primary task immediately after the attack. In counseling the rape victim, it is important to understand her individual style of coping, to be supportive of it, and to suggest alternatives for future stressful situations.
Ezh2 loss in hematopoietic stem cells predisposes mice to develop heterogeneous malignancies in an Ezh1-dependent manner
Authors: Makiko Mochizuki-Kashio, Kazumasa Aoyama, Goro Sashida, Motohiko Oshima, Takahisa Tomioka, Tomoya Muto, Changshan Wang, Atsushi Iwama
Journal: Blood (2015)
Maternal asthma phenotypes and children's allergy status
Authors: Maria Vakharlovskaya, Olga Lavrova, Maria Petrova
Journal: European Respiratory Journal (2011)

Background: Asthma is a complex heterogeneous disease comprising a number of discrete phenotypes. Allergy status in children tends to differ according to asthmatic phenotype of parents, particularly mothers. Mother's asthmatic phenotype stipulates for differences in structure and time of allergy onset in children.

Purpose: To study the influence of maternal asthma phenotype on children's allergy status.

Methods: We evaluated the allergy status in children from birth to 7 years of age born from 117 asthmatic mothers with regard to their asthma phenotypes; 88 (75.2%) mothers had early onset asthma phenotype (defined as asthma developing before 16 years of age), 29 (24.8%) – late onset phenotype.

Results: The prevalence of allergic asthma and other allergic forms (allergic rhinitis and atopic dermatitis) in children by 7 years of life differed (p<0.001, binomial test) depending on the onset asthma phenotypes of mothers. Children born from mothers with early onset asthma phenotypes will be at higher asthma and others allergic forms risk (OR=3,04 [CI: 1.013-9.132]).

Conclusions: Maternal asthma phenotype influences the onset and structure of allergy in children. Understanding of underlying asthma genesis is needed for protective measures and prognosis of the diseases in children.
Abstract 5317: Bone Morphogenetic Protein Recruits a Peroxisome Proliferator-Activated Receptor {gamma} and {beta}-catenin Transcription Factor Complex to Regulate Apelin Expression in Pulmonary Endothelial Cells
Authors: Tero-Pekka Alastalo, Molong Li, Vinicio de Jesus Perez, Hirofumi Sawada, Marlene Rabinovitch
Journal: Circulation (2009)

Our previous studies on the pathobiology of pulmonary arterial hypertension (PAH) demonstrated that bone morphogenetic protein receptor II (BMPRII) mediated signaling plays a key role in pulmonary ...
Statistics Notes: Diagnostic tests 1: sensitivity and specificity
Authors: D G Altman, J M Bland
Journal: BMJ (1994)

The simplest diagnostic test is one where the results of an investigation, such as an x ray examination or biopsy, are used to classify patients into two groups according to the presence or absence of a symptom or sign. For example, the table shows the relation between the results of a test, a liver scan, and the correct diagnosis based on either necropsy, …
Usefulness of medical oncologists’ estimates of survival time in people with advanced cancer.
Authors: Belinda E. Kiely, Andrew J. Martin, Martin HN Tattersall, Anna K. Nowak, David Goldstein, Nicholas Wilcken, David Wyld, Philip James Beale, Michael Jefford, Amanda L. Glasgow, Ehtesham A. Abdi, Paul A. Glare, Martin R. Stockler
Journal: Journal of Clinical Oncology (2012)

9087 Background: We sought to determine the calibration, precision, prognostic significance and suitability of estimated survival time (EST) as a basis for estimating and explaining prognosis in advanced cancer. Methods: Medical oncologists recorded their EST as the “median survival of a group of identical patients” in patients with advanced cancer and a life expectancy &gt;3 months recruited to a randomized trial of sertraline (Lancet Oncol 2007; 8: 603). Calibration, precision and suitability were defined by the proportions of patients whose observed survival times (OST) were bounded by simple multiples of their EST (based on our previous studies), i.e. 50% expected to live longer (or shorter) than their EST; 30% expected to live from 0.75 to 1.33 times their EST (arbitrary criterion for precision); 50% expected to live from half to double their EST (range for typical scenario); 10% expected to live &gt;3 times their EST (best case scenario), or &lt;¼ of their EST (worst case scenario). Results: Characteristics of the 114 patients were: median age 63 years, Karnofsky performance status (KPS) ≤70 in 25%, and a median of 8.5 months since diagnosis of advanced cancer. Primary cancer sites included breast (18%), colorectal (16%), lung (15%), prostate (12%) and ovary (10%). Median survival was 10.6 months after a median follow-up of 14 months and 68 deaths. EST were well-calibrated: 54% of patients lived longer than their EST and 46% lived shorter than their EST. EST were imprecise (21% within 0.75 to 1.33 times OST) but equally likely to be over-optimistic (34% &gt;1.33 x OST) or over-pessimistic (39% &lt;0.75 x OST). 6% of patients lived &lt;¼ of their EST; 62% lived from half to double their EST and 9% lived &gt;3 times their EST. Independently significant predictors of OST in a multivariable Cox model included EST (HR=0.92, p=0.004), dry mouth (HR=5.07, p&lt;0.0001), alkaline phosphatase &gt;101U/L (HR=2.80, p=0.0002), KPS ≤70 (HR=2.30, p=0.007), prostate primary (HR=0.23, p=0.002), and steroid use (HR=2.35, p=0.02). Conclusions: Medicaloncologists’ EST were well-calibrated, imprecise, independently associated with OST, and useful for estimating and explaining best case, worse case, and typical scenarios for survival time in patients with advanced cancer.
Personality features of obsessive-compulsive disorder
Authors: R T Joffe, R P Swinson, J J Regan
Journal: American Journal of Psychiatry (1988)

The authors evaluated personality dysfunction in 23 patients with primary obsessive-compulsive disorder and an age- and sex-matched group of patients with major depressive disorder. There were no significant differences between the two patient groups with respect to mean personality trait scores or the frequency or type of personality disorder diagnosis. A mixed personality disorder with avoidant, dependent, and passive-aggressive features was most commonly observed in the obsessive-compulsive group. There was a very low frequency of schizoid or compulsive personality disorder.
Effects of Partial Left Ventriculectomy on Cardiac Performance
Authors: Kiyotaka Fukamachi, Patrick M. McCarthy, Randall C. Starling, James B. Young
Journal: Circulation (1998)

The statement on "Phytochemicals and Cardiovascular Disease" published in the June 3, 1997, issue of Circulation 1 focuses attention on the vast therapeutic possibilities found in plants.One of the 3 groups of substances mentioned, the flavonoids, is found in great abundance in standardized special extracts of Hawthorn leaves with flowers.This extract has been studied extensively in Germany and is currently being used as a treatment modality in NYHA class II heart failure.Clinical studies (double-blind and placebo controlled) have been published in German and other languages 2,3 along with pharmacological and chemical studies.In a recent article, 4 136 patients (NYHA class II heart failure) were randomized (double-blind) to either 160 mg Hawthorn special extract WS 1442 per day or placebo.The difference between the pressure/heart rate product (PHRP) at a 50-W load versus rest was measured before and after treatment, and the change in this parameter was defined as the primary target parameter.The group receiving active medication showed a significant improvement in the PHRP, whereas, in the placebo group, this parameter tended to deteriorate.Other surrogate parameters (patients' subjective assessment of symptoms and quality of life) also improved.The medication was excellently tolerated.The cardioprotective qualities of Hawthorn extract WS 1442 have been demonstrated by Krzeminski and Chatterjee. 5 They used the ischemia/reperfusion model in 2 groups of rats, 1 receiving 100 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 of the standardized Hawthorn extract WS 1442 orally for 6 days before induction of ischemia and the other serving as a control group.Active treatment effectively protected the animals from reperfusion-induced arrhythmia, mortality, and hypotensive crisis, as observed in the control animals after 7 minutes of coronary occlusion.A better understanding of the pharmacological working principles of WS 1442 is offered by Chatterjee et al. 6 They fractionated the Hawthorn extract and demonstrated that a subgroup of the flavonoids, namely, the oligomeric procyanidins, possess potent radical scavenging and human neutrophil elastase inhibitory activities.Further research is being carried out with this special Hawthorn extract to investigate its pharmacological properties and its clinical significance, not only in early but also in advanced stages of heart failure and for secondary prevention after myocardial infarction.
Tissue analysis of solitary pulmonary nodules using OCT A-Scan imaging needle probe
Authors: Lukas Wittig, Christoph Otte, Sebastian Otte, Gereon Hüttmann, Daniel Drömann, Alexander Schlaefer
Journal: European Respiratory Journal (2014)

State of the art to specify the entity of solitary pulmonary nodules (SPN) is TTNA or TBNA. Optical coherence tomography (OCT) has the capability to close the gap between confocal microscopy and ultrasound.  To investigate OCT imaging in the diagnosis of SPN′s we developed a forward imaging needle probe. Single A-Scan images were taken from different tissue sides manually and consecutive A-Scans while puncturing robotically guided.  Histopathology defined the tissue probe as malignant or nonmalignant and characterized the architecture of the lung and SPN along the robotically punctured channel. The A-Scans were classified by a bidirectional long short term memory network. From 15 different tissue specimens 75 datasets of lung tissue and 22 datasets of tumor tissue have been acquired. Results are shown in Figure 1 [1 and 2: A-Scans from the same patient contribute to test set or trainings set. All tumor samples (PatAll), adeno carcinoma (PatAd). 3 and 4: A-Scans from the same record contribute to test set or training set. All carcinoma (RecAll), adeno carcinoma (RecAd)]. Further analysis of the individual patient data showed improved sensitivity, specificity and accuracy.  Our results demonstrate that individual OCT A-Scans can provide information for differentiation of malignant and non-malignant lung tissue. Further were we able to align histopathologic features and OCT features of the consecutive data sets.
Abstract 4198: cAMP signaling in BRAFV600E melanoma
Authors: Carlos I. Rodriguez
Journal: Cancer Research (2014)

Abstract G-protein coupled receptor (GPCR) signaling, predominantly the cyclic AMP (cAMP) signaling, is crucial for melanocyte proliferation and differentiation. Previous studies have shown a downregulation in cAMP signaling in mutant NRAS melanoma. However, no relationship has been reported about cAMP signaling in mutant BRAF melanoma, which makes up about 60% of all cutaneous melanoma. Here, we studied the role of four main G-protein signaling pathways using reporters for Gαs (cAMP Response Element, CRE), Gαq (inositol triphosphate signaling, NFAT-RE), Gα12 (RhoA signaling, SRF-RE) and Gβγ (MAPK pathway, SRE), in melanoma. Our data show that cAMP signaling is substantially more constitutively active in BRAFV600E mutant melanoma than NRAS mutant melanoma. Moreover, hyperactivation of cAMP signaling decreases proliferation and migration in BRAFV600E. Interestingly, in a melanoma cell line with neither BRAF nor NRAS mutation, cAMP hyperactivation increased proliferation. Furthermore, BRAFV600E inhibition increases constitutive cAMP activity. These results show a possible crosstalk between cAMP signaling and BRAFV600E in melanoma. Citation Format: Carlos I. Rodriguez. cAMP signaling in BRAFV600E melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4198. doi:10.1158/1538-7445.AM2014-4198
Patient-specific cardiovascular progenitor cells derived from integration-free induced pluripotent stem cells for vascular tissue regeneration
Authors: Jiang Hu, Yongyu Wang, Jiao Jiao, Zhongning Liu, Chao Zhao, Zhou Zhou, Zhanpeng Zhang, Kaitlynn Forde, Lunchang Wang, Jiangang Wang, David J. Baylink, Xiao-Bing Zhang, Shaorong Gao, Bo Yang, Y. Eugene Chen, Peter X. Ma
Journal: Biomaterials (2015)
Propranolol for infantile haemangiomas: insights into the molecular mechanisms of action
Authors: C.H. Storch, P.H. Hoeger
Journal: British Journal of Dermatology (2010)

Infantile haemangiomas (IH) are the most common benign tumours of infancy. Although most IH are innocuous and 85-90% regress spontaneously, some may become life- or function-threatening and require immediate treatment. Previous standard therapeutic options include physical measures (laser surgery, cryosurgery) and systemic corticosteroids, in severe cases also vincristine, alpha-interferon or cyclophosphamide, all bearing the risk of serious side-effects. Oral propranolol is a very recent therapeutic option for complicated IH with impressive efficacy and generally good tolerance. The effects of propranolol on IH were discovered by chance, and very little is known about its mechanisms of action in IH. Here we present a summary of current knowledge of how propranolol interferes with endothelial cells, vascular tone, angiogenesis and apoptosis. Early, intermediate and long-term effects of propranolol on IH can be attributed to three different pharmacological targets. Early effects (brightening of the haemangioma surface within 1-3 days after start of therapy) are attributable to vasoconstriction due to decreased release of nitric oxide. Intermediate effects are due to the blocking of proangiogenic signals (vascular endothelial growth factor, basic fibroblast growth factor, matrix metalloproteinase 2/9) and result in growth arrest. Long-term effects of propranolol are characterized by induction of apoptosis in proliferating endothelial cells, and result in tumour regression.
Validating SIK as a novel COPD target using four different human systems
Authors: Melker Göransson, Ulf Hedström, Barbara Fuchs
Journal: European Respiratory Journal (2014)

Recent findings identify salt inducible kinases (SIKs) as a key molecular switch, whose inhibition reprograms murine macrophages to an anti-inflammatory phenotype. The underlying chronic inflammation of the airways, triggered by the inhalation of noxious substances such as tobacco smoke, leads to structural changes and narrowing of the small airways in COPD. This inflammatory state is believed to be driven primarily by macrophages, T-lymphocytes and neutrophils. Polarization of macrophages into a regulatory population, that produces high levels of IL-10 and low levels of pro-inflammatory cytokines like TNFa, may play an important role in the resolution of inflammation and is hypothesized to reduce frequency of COPD exacerbations.  We have set up assays in four different human systems ranging from THP-1 cells, monocyte-derived macrophages and alveolar macrophages, to lung explant cultures for validation of this target in a human setting.  Our data from both “normal” primary cells/tissue from cancer resections as well as COPD derived primary cells/tissue show that the concept of changing the TNFa/IL10 ratio, and thus the inflammatory state of the lung, by inhibiting SIK is conserved from mice to man. However, the level of expression differs between species and the effect is more modest in a human system.  The SIK family consists of 3 members and it is not yet fully clear which of the SIK1-3 proteins is important for polarization of macrophages, but recent evidence suggests SIK2 as being the major target in the mouse system. In parallel with the standard target validation strategies, the effect of mutating strategic phosphorylation sites on SIK1-3 in a human cell line will be assessed using TALEN technology.
HOT HMV UK: An investigation into mechanisms of action of home mechanical ventilation (HMV) following acute hypercapnic exacerbations of COPD
Authors: Patrick Murphy, John Moxham, Michael Polkey, Nicholas Hart
Journal: European Respiratory Journal (2011)

Introduction:  HMV in COPD remains controversial. Current data indicates improvements in arterial carbon dioxide (PaCO 2 ) are mediated by improved pulmonary mechanics and hypercapnic ventilatory response (HCVR). This hypothesis has yet to be tested in a controlled trial and no studies have investigated changes in neural respiratory drive (NRD) measured by parasternal EMG (EMG para ).   Method:  Patients with persistent hypercapnia (PaCO 2  >7 kPa) 2-4 weeks after resolution of an acute exacerbation of COPD were randomised to home oxygen therapy (HOT) or HOT and HMV. Baseline studies included HCVR and EMG para . Patients were re-studied at 6 weeks.   Results:  20 patients have been recruited and randomised.  Follow up data is presented on 9 patients. Ventilator settings were IPAP 28±3, EPAP 5±1, RR 15±1. Significant improvement in both PaO 2  and PaCO 2  only occurred in the HMV group.  There was a significant between group difference in HCVR and NRD.   Conclusion:  These preliminary data suggest that the addition of HMV to HOT in this group is associated with improvements in gas exchange and this appears in part mediated by changes in HCVR and NRD suggesting “resetting” of central drive.
Adrenergic Modulation of Pancreatic A, B, and D Cells
Authors: Ellis Samols, Gordon C. Weir
Journal: Journal of Clinical Investigation (1979)

The effects of adrenergic substances on pancreatic insular secretions were studied in a completely isolated canine pancreas with exclusion of the duodenum from the perfusion circuit. To ensure adequate blockade, blockers were infused before agonists. A dose range of β-receptor blockade was tested, and putative α-adrenergic effects were confirmed by combined α- and β-adrenergic receptor blockade.
Abstract 12011: Super-Responders to CRT: The Golden Hour Could be the Right Question
Authors: Gabriele Borelli, Maria Rosaria Ferraro, Nicola Scelza, Paola Bendinelli, Giovanni Benedetti, Maria Grazia Bongiorni, Lorenzo Rondinini, Rita Mariotti
Journal: Circulation (2011)

Aims:  Despite the current selection criteria, individual response to cardiac resynchronization therapy (CRT) varies significantly. A minority of patients show an excellent clinical and functional improvement after CRT. These patients are called super-responders. The aim of our study was to identify predictors of becoming a super-responder after CRT and to assess the survival benefit associated with this response.   Methods and results:  Eighty-nine consecutive patients in optimized medical therapy (mean age 69±9years, male 71%, NYHA 3.1±0.6, LVEF 26.8±6.3%) who underwent CRT were prospectively studied. Before CRT and 6-12-24-48 months after, clinical and echocardiographic evaluation were performed. Patients with a 12 months decrease in NYHA functional class ≥1 and an absolute increase of LVEF ≥5 were classified as clinical (CR) and functional responders (FR), respectively; an absolute improvement in LVEF>10 was used to define super-responders (SR). We observed 74, 43 and 26% of CR, FR and SR, respectively. In SR group the 85% was also CR, while in CR group only 29% was also SR. At baseline SR showed an higher prevalence of primitive etiology (39 vs 17%, p   Conclusion:  Patients in earlier phases of the cardiomyopathy, with a less altered ventricular geometry and a more preserved diastolic filling, seem to have a greater probability of becoming SR. The SR long-term prognosis is strongly better than all other CRT responders patients, either CR either RF.