tbuckley/cabot-search huggingface dataset:
Usefulness of data from magnetic resonance imaging to improve prediction of dementia: population based cohort study
Authors: B. C. M. Stephan, C. Tzourio, S. Auriacombe, H. Amieva, C. Dufouil, A. Alperovitch, T. Kurth
Journal: BMJ (2015)

<b>Objective</b> To determine whether the addition of data derived from magnetic resonance imaging (MRI) of the brain to a model incorporating conventional risk variables improves prediction of dementia over 10 years of follow-up. <b>Design</b> Population based cohort study of individuals aged ≥65. <b>Setting</b> The Dijon magnetic resonance imaging study cohort from the Three-City Study, France. <b>Participants</b> 1721 people without dementia who underwent an MRI scan at baseline and with known dementia status over 10 years' follow-up. <b>Main outcome measure</b> Incident dementia (all cause and Alzheimer's disease). <b>Results</b> During 10 years of follow-up, there were 119 confirmed cases of dementia, 84 of which were Alzheimer's disease. The conventional risk model incorporated age, sex, education, cognition, physical function, lifestyle (smoking, alcohol use), health (cardiovascular disease, diabetes, systolic blood pressure), and the apolipoprotein genotype (C statistic for discrimination performance was 0.77, 95% confidence interval 0.71 to 0.82). No significant differences were observed in the discrimination performance of the conventional risk model compared with models incorporating data from MRI including white matter lesion volume (C statistic 0.77, 95% confidence interval 0.72 to 0.82; P=0.48 for difference of C statistics), brain volume (0.77, 0.72 to 0.82; P=0.60), hippocampal volume (0.79, 0.74 to 0.84; P=0.07), or all three variables combined (0.79, 0.75 to 0.84; P=0.05). Inclusion of hippocampal volume or all three MRI variables combined in the conventional model did, however, lead to significant improvement in reclassification measured by using the integrated discrimination improvement index (P=0.03 and P=0.04) and showed increased net benefit in decision curve analysis. Similar results were observed when the outcome was restricted to Alzheimer's disease. <b>Conclusions</b> Data from MRI do not significantly improve discrimination performance in prediction of all cause dementia beyond a model incorporating demographic, cognitive, health, lifestyle, physical function, and genetic data. There were, however, statistical improvements in reclassification, prognostic separation, and some evidence of clinical utility.
A tumor necrosis factor (TNF) receptor-IgG heavy chain chimeric protein as a bivalent antagonist of TNF activity.
Authors: K Peppel, D Crawford, B Beutler
Journal: The Journal of Experimental Medicine (1991)

Using a multistep polymerase chain reaction method, we have produced a construct in which a cDNA sequence encoding the extracellular domain of the human 55-kD tumor necrosis factor (TNF) receptor is attached to a sequence encoding the Fc portion and hinge region of a mouse IgG1 heavy chain through an oligomer encoding a thrombin-sensitive peptide linker. This construct was placed downstream from a cytomegalovirus promoter sequence, and expressed in Chinese hamster ovary cells. A secreted protein, capable of binding TNF and inactivating it, was produced by the transfected cells. Molecular characterization revealed that this soluble version of the TNF receptor was dimeric. Moreover, the protein could be quantitatively cleaved by treatment with thrombin. However, the monovalent extracellular domain prepared in this way has a greatly reduced TNF inhibitory activity compared with that of the bivalent inhibitor. Perhaps because of its high affinity for TNF, the chimeric protein is far more effective as a TNF inhibitor than are neutralizing monoclonal antibodies. This molecule may prove very useful as a reagent for the antagonism and assay of TNF and lymphotoxin from diverse species in health and disease, and as a means of deciphering the exact mechanism through which TNF interacts with the 55-kD receptor.
The CD40/CD40L axis in glioma progression and therapy
Authors: Paul R. Walker, Denis Migliorini
Journal: Neuro-Oncology (2015)

Generation or enhancement of immune responses through engagement of costimulatory receptors such as CD40 ligation is an essential component of antitumor immunity and could be exploited in glioma immunotherapy. Nevertheless, the importance of adequate immune stimulation is somewhat overshadowed by the current rush towards blocking immune inhibition using checkpoint-blockade antibodies. Therefore, the current study by Chonan et al1 in which CD40/CD40L expression and manipulation are revisited in glioma is a useful reminder of the stimulatory component of antiglioma immunity.
THE VASCULAR BIOLOGY OF NITRIC OXIDE AND ITS ROLE IN ATHEROGENESIS
Authors: Donald M. Lloyd-Jones, M.D, Kenneth D. Bloch, M.D
Journal: Annual Review of Medicine (1996)

▪ Abstract Nitric oxide (NO), the biologically active component of endothelium-derived relaxing factor, has critical roles in the maintenance of vascular homeostasis. Decreased endothelial NO production, as a result of endothelial dysfunction, occurs in the early phases of atherosclerosis. NO appears to inhibit atherogenesis by inhibiting leukocyte and platelet activation and by inhibiting smooth muscle cell proliferation. Endothelial denudation is a prominent feature of vascular injury associated with percutaneous angioplasty, and decreased NO production appears to contribute to the restenosis process. Manipulation of the NO/cGMP signal transduction system may provide novel therapeutic approaches for limiting atherogenesis and neointimal proliferation in the future.
Assessing and helping carers of older people
Authors: I. D. Cameron, C. Aggar, A. L. Robinson, S. E. Kurrle
Journal: BMJ (2011)

#### Summary points

Carers are an essential source of support to older people and take responsibility for most of their care needs. Although many carers find aspects of the caring role satisfying,1 caring responsibilities can lead to a decline in their own physical and mental health1 2 3—especially when caring for those with dementia4—and adversely affect their employment and education prospects, financial position, and ability to participate in social and community life.2 It is therefore important to identify people who have an important informal caring role. An assessment of the carer and his or her individual needs, and of the caregiving situation, can improve the health and wellbeing of the carer and ensure the provision of timely and appropriate support services.1

#### Sources and selection criteria

As well as using our personal reference collections, we searched the Cochrane database and reviewed guidelines from the National Institute …
Numerical abstraction: It ain't broke
Authors: Jessica F. Cantlon, Sara Cordes, Melissa E. Libertus, Elizabeth M. Brannon
Journal: Behavioral and Brain Sciences (2009)

Abstract The dual-code proposal of number representation put forward by Cohen Kadosh &amp; Walsh (CK&amp;W) accounts for only a fraction of the many modes of numerical abstraction. Contrary to their proposal, robust data from human infants and nonhuman animals indicate that abstract numerical representations are psychologically primitive. Additionally, much of the behavioral and neural data cited to support CK&amp;W's proposal is, in fact, neutral on the issue of numerical abstraction.
The Obstetrician Bids, and the Uterus Contracts
Authors: J. C. Moir
Journal: BMJ (1964)

We are in a century of change.Nowhere is this more true than in medical, and especially obstetrical, practice.I myself remember the constant fear of puerperal sepsis which made my teachers reluctant to resort to even simple interference with the natural course of childbirth.Rachitic deformities were still distressingly prevalent, and the older men could recall the days when, in the Glasgow Maternity Hospital, for example, no less than one in every 30 deliveries was effected by craniotomy.Let me put this change into figures.For every 15 women who, even 30 years ago, died in childbirth, to-day only one is numbered.Turning to post-partum haemorrhage-the subject toward which this lecture will be specially directed- for every 10 women who then died in childbirth only one dies to-day.The mortality of post-partum haemorrhage has thus decreased tenfold.What answer can we give to the obvious questions: Why ? and How ?It would be easy-it would also be misleading-to give a single, simple answer.Many factors have collectively brought about the change.Let me enumerate some of them: better general health of the parturient woman; better obstetrical technique; better means of combating infection which so often follows haemorrhage; better means of replacing lost blood- and here let me remind you that it was one of the major advances of the century when, under the stimulus of the second world war, blood banks were established throughout the length and breadth of the country, and simplified methods devised of effecting safe and adequate transfusion.Collectively, these are the ways in which obstetric practice has advanced.And yet there is another factor which has probably contributed as much as any to a reduction of the mortality from haemorrhage.This is the introduction and general availability of reliable drugs which cause the uterus to contract and which check post-partum haemorrhage or even prevent it before it has appeared.Chief among these is ergot.
Comparison of the responsiveness of the Harris Hip Score with generic measures for hip function in osteoarthritis of the hip
Authors: H L Hoeksma
Journal: Annals of the Rheumatic Diseases (2003)

To compare responsiveness of the Harris Hip Score with generic measures (that is, the Short Form-36 (SF-36), and a test of walking speed and pain during walking) in patients with osteoarthritis (OA) of the hip.The first 75 cases within the population of a randomised clinical trial on manual therapy and exercise therapy were selected for secondary analysis. Experienced (self reported) recovery by the patients after treatment (five weeks) was used as an external criterion for clinically relevant improvement. Responsiveness was evaluated by comparing responsiveness ratios and receiver operating characteristic curves.The responsiveness ratio for the Harris Hip Score was high (1.70) compared with walking speed (0.45), pain during walking (0.66), and the subscales of the SF-36-"bodily pain" (0.42) and "physical functioning" (0.36). The area under the curve also was highest for the Harris Hip Score (0.92) compared with walking speed (0.71), pain during walking (0.73), and the SF-36 subscales-bodily pain and physical functioning (both 0.66).The Harris Hip Score is more responsive than the test of walking speed, pain, and subscales for function of the SF-36 in patients with OA of the hip. The Harris Hip Score seems to be a suitable instrument to evaluate change in hip function in patients with OA of the hip.
Novel Clinical Markers of Vascular Wall Inflammation
Authors: Gavin J. Blake, Paul M. Ridker
Journal: Circulation Research (2001)

Inflammatory processes play a pivotal role in the pathogenesis of atherosclerosis and mediate many of the stages of atheroma development from initial leukocyte recruitment to eventual rupture of the unstable atherosclerotic plaque. Elevated plasma levels of several markers of the inflammatory cascade have been shown to predict future risk of plaque rupture. These markers include P-selectin, interleukin-6, tumor necrosis factor-α, soluble intercellular adhesion molecule-1, and C-reactive protein (CRP). Produced in the liver in response to interleukin-6, CRP has emerged as the most powerful inflammatory marker of future cardiovascular risk. Initially considered an innocent bystander in the atherosclerotic process, recent evidence suggests that CRP may have direct proinflammatory effects. Numerous large-scale, prospective studies have found that elevated baseline levels of CRP are a strong independent predictor of future vascular risk. Furthermore, aspirin and statin therapy appear to be particularly effective among individuals with high CRP levels. The addition of CRP screening to traditional lipid testing has the potential to identify individuals at high risk for future cardiovascular events who may benefit from targeted preventive interventions.
Melanoma Cells Inhibit NK Cell Functions—Response
Authors: Gabriella Pietra, Massimo Vitale, Claudia Manzini, Mirna Balsamo, Lorenzo Moretta, Maria Cristina Mingari
Journal: Cancer Research (2012)

We appreciated the comments by Sconocchia and colleagues to our recent study describing a novel tumor escape mechanism that allows melanoma cells to prevent natural killer (NK)-mediated recognition and killing ([1][1]). 

We agree with the authors that the altered receptor expression and the limited
Regulation of osteoclast function and bone mass by RAGE
Authors: Zheng Zhou, David Immel, Cai-Xia Xi, Angelika Bierhaus, Xu Feng, Lin Mei, Peter Nawroth, David M. Stern, Wen-Cheng Xiong
Journal: The Journal of Experimental Medicine (2006)

The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily that has multiple ligands and is implicated in the pathogenesis of various diseases, including diabetic complications, neurodegenerative disorders, and inflammatory responses. However, the role of RAGE in normal physiology is largely undefined. Here, we present evidence for a role of RAGE in osteoclast maturation and function, which has consequences for bone remodeling. Mice lacking RAGE had increased bone mass and bone mineral density and decreased bone resorptive activity in vivo. In vitro–differentiated RAGE-deficient osteoclasts exhibited disrupted actin ring and sealing zone structures, impaired maturation, and reduced bone resorptive activity. Impaired signaling downstream of αvβ3 integrin was observed in RAGE−/− bone marrow macrophages and precursors of OCs. These results demonstrate a role for RAGE in osteoclast actin cytoskeletal reorganization, adhesion, and function, and suggest that the osteosclerotic-like phenotype observed in RAGE knockout mice is due to a defect in osteoclast function.
Fibroepithelioma of Pinkus is a true basal cell carcinoma developing in association with a newly identified tumour-specific type of epidermal hyperplasia
Authors: K. Sellheyer, P. Nelson, H. Kutzner
Journal: British Journal of Dermatology (2011)

Fibroepithelioma of Pinkus (FEP) has long been viewed as a subtype of basal cell carcinoma (BCC). Recently, however, the proposal has been made that FEP represents a fenestrated trichoblastoma/trichoepithelioma. One of the main arguments is the presence of Merkel cells in FEP, which typically do not occur in BCC.As the new stem cell marker, PHLDA1 (TDAG51), labels trichoepithelioma but not BCC, our aim was to characterize its staining pattern in FEP. Because adnexal tumours have been viewed as recapitulating embryogenesis, we also examined PHLDA1 immunoreactivity in the skin of human embryos and fetuses.We studied immunohistochemically PHLDA1 staining in 31 FEPs, 14 BCCs and 16 trichoepitheliomas and compared this with its staining pattern in embryonic skin and with the distribution of Merkel cells.In FEP, PHLDA1 labels the anastomosing network of thin cellular strands but not the basaloid nubbins. During embryogenesis, PHLDA1 stains the basal cell layer of the epidermis, as long as adnexal structures develop. Immunoreactivity for PHLDA1 correlates positively with the presence of Merkel cells.We propose that the thin anastomosing network of PHLDA1-positive cells represents a type of epidermal hyperplasia specific to FEP. The multifocal BCCs that are PHLDA1-negative develop from this network which becomes incorporated into the tumour. Viewing the anastomosing network as a tumour-specific form of epidermal hyperplasia explains the hitherto enigmatic presence of Merkel cells in FEP.
Effects of Dimethylsulfoxide on Expression of Differentiated Functions in Mouse Neuroblastoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Philip Furmanski, Martin Lubin
Journal: JNCI Journal of the National Cancer Institute (1972)

Dimethylsulfoxide (DMSO) reversibly inhibited extension of neuntes in mouse neuroblastoma cells in vitro at levels which did not significantly retard growth. This inhibition occurred when neuntes were induced to extend either by removal of serum or by addition of dibutyrylcyclic adenosine monophosphate to complete medium. Inhibition was reversed with time, however, even in the continued presence of DMSO in serum-free medium. At similar concentrations of DMSO in serum-free medium, induction of acetylcholinesterase activity was not inhibited.
Potential for bias in epidemiologic studies that rely on glass-based retrospective assessment of radon.
Authors: C R Weinberg
Journal: Environmental Health Perspectives (1995)

Retrospective assessment of exposure to radon remains the greatest challenge in epidemiologic efforts to assess lung cancer risk associated with residential exposure. An innovative technique based on measurement of alpha-emitting, long-lived daughters embedded by recoil into household glass may one day provide improved radon dosimetry. Particulate air pollution is known, however, to retard the plate-out of radon daughters. This would be expected to result in a differential effect on dosimetry, where the calibration curve relating the actual historical radon exposure to the remaining alpha-activity in the glass would be different in historically smoky and nonsmoky environments. The resulting
Effects of infection control measures on acquisition of five antimicrobial drug-resistant microorganisms in a tetanus intensive care unit in Vietnam
Authors: Constance Schultsz, Martinus C. J. Bootsma, Huynh T. Loan, Tran T. T. Nga, Le T. P. Thao, Tran T. D. Thuy, James Campbell, Le M. Vien, Ngo T. Hoa, Nguyen V. M. Hoang, Ferdinand Wit, Nguyen V. V. Chau, Jeremy Farrar, Marc J. M. Bonten, Lam M. Yen
Journal: Intensive Care Medicine (2013)

To quantify the effects of barrier precautions and antibiotic mixing on prevalence and acquisition of five drug-resistant microorganisms within a single tetanus intensive care unit at a tertiary referral hospital in Ho Chi Minh City, Vietnam.All patients admitted within the study period were included. After a 1-year baseline period, barrier precautions were implemented and the single empirical treatment ceftazidime was changed to mixing (per consecutive patient) of three different regimens (ceftazidime, ciprofloxacin, piperacillin-tazobactam). Markov chain modeling and genotyping were used to determine the effects of interventions on prevalence levels and the relative importance of cross-transmission and antibiotic-associated selection.A total of 190 patients were included in year 1 (2,708 patient days, 17,260 cultures) and 167 patients in year 2 (3,384 patient days, 20,580 cultures). In year 1, average daily prevalence rates for methicillin-resistant Staphylococcus aureus (MRSA), extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (excluding Klebsiella pneumoniae), Pseudomonas aeruginosa, gentamicin-resistant K. pneumoniae, and amikacin-resistant Acinetobacter species were 34.0, 61.3, 53.4, 65.7 and 57.1 %. After intervention, ceftazidime usage decreased by 53 %; the use of piperacillin-tazobactam and ciprofloxacin increased 7.2-fold and 4.5-fold, respectively. Adherence to hand hygiene after patient contact was 54 %. These measures were associated with a reduction of MRSA prevalence by 69.8 % (to 10.3 %), mainly because of less cross-transmission (88 % reduction), and of ESBL-producing Enterobacteriaceae prevalence by 10.3 % (non-significantly). In contrast, prevalence levels of the other three pathogens remained unaffected.The combination of simple infection control measures and antibiotic mixing was highly effective in reducing the prevalence of MRSA, but not of Gram-negative microorganisms.
A Phase I Dose-Escalation and Pharmacokinetic Study of S-1 Plus Nab-Paclitaxel in Patients with Unresectable or Recurrent Gastric Cancer
Authors: Ishido Kenji, Nakayama Norisuke, Chin Keisho, Higuchi Katsuhiko, Nishimura Ken, Matsusaka Satoshi, Azuma Mizutomo, Takagi Seiichi, Kumekawa Yosuke, Tanabe Satoshi, Inokuchi Yasuhiro, Koizumi Wasaburo
Journal: Annals of Oncology (2014)
Blood lipid and lipoprotein concentrations and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition
Authors: F. J. B. van Duijnhoven, H. B. Bueno-De-Mesquita, M. Calligaro, M. Jenab, T. Pischon, E. H. J. M. Jansen, J. Frohlich, A. Ayyobi, K. Overvad, A. P. Toft-Petersen, A. Tjonneland, L. Hansen, M.-C. Boutron-Ruault, F. Clavel-Chapelon, V. Cottet, D. Palli, G. Tagliabue, S. Panico, R. Tumino, P. Vineis, R. Kaaks, B. Teucher, H. Boeing, D. Drogan, A. Trichopoulou, P. Lagiou, V. Dilis, P. H. M. Peeters, P. D. Siersema, L. Rodriguez, C. A. Gonzalez, E. Molina-Montes, M. Dorronsoro, M.-J. Tormo, A. Barricarte, R. Palmqvist, G. Hallmans, K.-T. Khaw, K. K. Tsilidis, F. L. Crowe, V. Chajes, V. Fedirko, S. Rinaldi, T. Norat, E. Riboli
Journal: Gut (2011)

<h3>Objective</h3> To examine the association between serum concentrations of total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol, triglycerides, apolipoprotein A-I (apoA), apolipoprotein B and the incidence of colorectal cancer (CRC). <h3>Design</h3> Nested case–control study. <h3>Setting</h3> The study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort of more than 520 000 participants from 10 western European countries. <h3>Participants</h3> 1238 cases of incident CRC, which developed after enrolment into the cohort, were matched with 1238 controls for age, sex, centre, follow-up time, time of blood collection and fasting status. <h3>Main outcome measures</h3> Serum concentrations were quantitatively determined by colorimetric and turbidimetric methods. Dietary and lifestyle data were obtained from questionnaires. Conditional logistic regression models were used to estimate incidence rate ratios (RRs) and 95% CIs which were adjusted for height, weight, smoking habits, physical activity, education, consumption of fruit, vegetables, meat, fish, alcohol, fibre and energy. <h3>Results</h3> After adjustments, the concentrations of HDL and apoA were inversely associated with the risk of colon cancer (RR for 1 SD increase of 16.6 mg/dl in HDL and 32.0 mg/dl in apoA of 0.78 (95% CI 0.68 to 0.89) and 0.82 (95% CI 0.72 to 0.94), respectively). No association was observed with the risk of rectal cancer. Additional adjustment for biomarkers of systemic inflammation, insulin resistance and oxidative stress or exclusion of the first 2 years of follow-up did not influence the association between HDL and risk of colon cancer. <h3>Conclusions</h3> These findings show that high concentrations of serum HDL are associated with a decreased risk of colon cancer. The mechanism behind this association needs further elucidation.
Transient ischemic dilation ratio of the left ventricle is a significant predictor of future cardiac events in patients with otherwise normal myocardial perfusion SPECT
Authors: Aiden Abidov, Jeroen J Bax, Sean W Hayes, Rory Hachamovitch, Ishac Cohen, James Gerlach, Xingping Kang, John D Friedman, Guido Germano, Daniel S Berman
Journal: Journal of the American College of Cardiology (2003)
Acute myeloid leukemia in patients previously diagnosed with breast cancer: Experience of the GIMEMA group
Authors: L. Pagano, A. Pulsoni, L. Mele, M.E. Tosti, R. Cerri, G. Visani, L. Melillo, A. Candoni, M. Clavio, A. Nosari, M.C. Petti, B. Martino, A. Mele, A. Levis, B. Allione, C. Almici, F. Equitani, G. Leone, F. Mandelli
Journal: Annals of Oncology (2001)